Pithoascus kurdistanensis: Discovery of a Novel Endophytic Fungal Species Associated with Papaver bracteatum, and its Production of Morphine Compounds

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Abstract Papaver genus, commonly known as popies, is a valuable source of alkaloids used in medicine, including papaverine, morphine, codeine, and thebaine. We isolated six endophytic fungal isolates producing morphinan alkaloids from four Papaver species growing in Kurdistan Province, Iran. To do this, a 1:1 mixture of methanol and chloroform was used to extract fungal cultures. The contents of morphinan alkaloids in the extracts were subsequently determined using phase high-performance liquid chromatography (HPLC). Among the morphinan alkaloid-producing fungal isolates, IRAN 4653C had the highest yield giving 23.06 (Mg/g) morphine and 2.03 (Mg/g) codeine when grown in potato dextrose liquid medium. Moreover, the morphinan productivity of IRAN 4653C was further validated by gas chromatography-mass spectrometry (GC-MS). The identity of this isolate was examined and recognized as a new fungal species named as Pithoascus kurdistanesis sp. nov. based on multi-gene phylogenetic analyses of ITS, TEF-1α, and TUB2 sequence data and morphological features. The morphinan-producing endophytic fungus and the isolated Pithoascus species from Papaver are being reported for the first time. Accordingly, this fungus shows promise as a new source of valuable compounds which is illustrated and introduced here as a new Microascaceae member belonging to Pithoascus from Kurdistan Province, Iran.
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Pithoascus kurdistanensis: Discovery of a Novel Endophytic Fungal Species Associated with Papaver bracteatum, and its Production of Morphine Compounds | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Pithoascus kurdistanensis: Discovery of a Novel Endophytic Fungal Species Associated with Papaver bracteatum, and its Production of Morphine Compounds Sima Mohammadi, Bahman Bahramnejad, Jafar Abdollahzadeh, Samaneh Bashiri, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4018361/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Sep, 2024 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Papaver genus, commonly known as popies, is a valuable source of alkaloids used in medicine, including papaverine, morphine, codeine, and thebaine. We isolated six endophytic fungal isolates producing morphinan alkaloids from four Papaver species growing in Kurdistan Province, Iran. To do this, a 1:1 mixture of methanol and chloroform was used to extract fungal cultures. The contents of morphinan alkaloids in the extracts were subsequently determined using phase high-performance liquid chromatography (HPLC). Among the morphinan alkaloid-producing fungal isolates, IRAN 4653C had the highest yield giving 23.06 (Mg/g) morphine and 2.03 (Mg/g) codeine when grown in potato dextrose liquid medium. Moreover, the morphinan productivity of IRAN 4653C was further validated by gas chromatography-mass spectrometry (GC-MS). The identity of this isolate was examined and recognized as a new fungal species named as Pithoascus kurdistanesis sp. nov. based on multi-gene phylogenetic analyses of ITS, TEF-1α, and TUB2 sequence data and morphological features. The morphinan-producing endophytic fungus and the isolated Pithoascus species from Papaver are being reported for the first time. Accordingly, this fungus shows promise as a new source of valuable compounds which is illustrated and introduced here as a new Microascaceae member belonging to Pithoascus from Kurdistan Province, Iran. Biological sciences/Microbiology/Fungi/Fungal biology Biological sciences/Microbiology/Fungi/Fungal evolution Microascaceae Pithoascus Papaver Morphinan alkaloids HPLC GC/MS Figures Figure 1 Figure 2 Introduction Benzylisoquinoline alkaloids (BIAs) are a group of specialized metabolites found in plants of the order Ranunculales, specifically in families like Papaveraceae . These compounds contain nitrogen and have various biological activities 1 . As secondary metabolites, BIAs are not crucial for normal growth and development, but they do play a crucial role in protecting plants against herbivores and pathogens. 2 . Tyrosine as a precursor of BIAs exhibits a wide range of pharmacological activities 3 . One subclass of benzylisoquinoline alkaloids is morphinan alkaloids, which are potent analgesics that have been used for thousands of years. These alkaloids are exclusively produced in plants of the Papaver genus. 4 . The Papaver genus is renowned for its production of various BIAs, including the potent painkiller morphine, the cough suppressant codeine, the muscle relaxant papaverine, an intermediate used in the semi-synthesis of other pentacyclic morphinan-based drugs, and the anti-microbial compound sanguinarine 5 . Nowadays, morphine and codeine continue to be the most beneficial and efficient compounds in medicine worldwide 6 . The intricate structures of morphinan, with five chiral centers, highlight the uneconomic commercial synthesis and cultivation of poppy as the most effective method for producing opiate analgesics 7 . Papaver as a genus (commonly known as poppy) belongs to the Papaveraceae family containing 830 species. These species are primarily found in temperate regions of the Northern Hemisphere, South Africa, and southern America 8 . Cullen (1966) reported 26 species of Papaver , including 5 that were endemic to Iran. However, this report did not take into account the sectional classification of the genus. More recent reports have identified species of this genus in various floristic regions of Iran 9,10 Papaver species can produce more than 170 different alkaloids, mainly in the form of benzylisoquinoline alkaloids (BIAs). Endophytes constitute any kind of organism that colonizes healthy plant tissue intercellularly and/or intracellularly, apparently without causing visible damage or morphological changes 11 . It is known that endophytic fungi live inside their host plant for protracted periods of time; the earliest records of them date back 400 million years. 12 . Endophytic fungi are a valuable and reputable source of bioactive and novel compounds with immense potential in the fields of medicine and agriculture. They also play a crucial role in enhancing the ecological adaptability of their host plants 13,14 . Interactions between plants and fungi can increase the production of bioactive metabolites in medicinal plants 15 . Also, some specified endophytic fungi mimic the host plant's secondary metabolites profile and tend to produce the plant medicinal products 16,17 such as taxol, camptothecin, and its structural analogs 18 , ginkgolide 19 . Therefore, researchers focusing on the isolation of endophytic fungi from pharmaceutical plants can discover many undescribed endophytic fungi species. Many of these fungi possess the ability to produce a diverse range of secondary metabolites that are associated with plants, exhibiting a wide array of biological activities. Endophytic fungi are frequently found within their host's metabolic networks, leading to changes in metabolite production and an increase in the presence of active compounds in medicinal plants 20 The evaluation of endophytic fungi plays a significant role in the production of bioactive metabolites which allows them to effectively adapt to their host and perform certain functions like synthesizing chemical compounds within these plants 21 . Researchers believe that the reason why endophytes produce certain chemical compounds is that genetic recombination occurred during evolution between the endophyte and its host 22,23 . This is the theory that was originally presented as an explanation for why the endophytic fungus Taxomyces andreanae should produce taxol 24 . Endophytic fungi in comparison with plants, grow much faster and are more appropriate for metabolic engineering 25 . Also, easier metabolites extraction from fungi could be valuable from both ecological and economic standpoints 24 . During a study on endophytic fungi associated with Papaver species and their secondary metabolite profiles for morphine alkaloids, we found a morphinan producing endophytic fungus placed in Pithoascus genus based on phylogenetic analyses of three loci (ITS, TEF-1α, TUB2) sequence data and morphological features. Pithoascus was established by Von Arx (1973) based on the type species P. nidicola , which formerly included in Microascus 26 . Some researchers based on morphology considered this genus as a synonym with Microascus but reinstated by Sandoval-Dennis et al. (2016) 27–30 based on a multi-gene (LSU, ITS, TEF-1α, TUB2) phylogenetic study. Pithoascus is a member of the Microascaceae family and is distinguished by ascomata with simple or barely noticeable ostioles and navicular to fusiform ascospores devoid of germ pores. Asexual morph produced in some species with single and laterally annellidic conidiogenous cells and globose to pyriform 1-celled solitary conidia 30 . According to Indexfungorum (June 2023; www.indexfungorum.org) and Mycobank (www.mycobank.org) nine species have been introduced in Pithoascus . These species are associated with humans (hair, nail, tinea plantaris), rat ( Dipodomys merriami ), wasps ( Megachile willughbiella, Osmia rufa ), soil and plants (e.g. Beta vulgaris , Fragaria vesca , Ferula ovina ) as saprophyte, endophyte and potential pathogen 30–32 . Here we introduce an endophytic fungus within Pithoascus genus as a new species and a taxonomic novelty for science which is able to produce morphinan species. This finding indicates the importance of microbial community associated with Papaver species as microbial potential sources to discover and produce new and valuable secondary metabolites. Results Isolation of fungi We collected 17 endophytic fungal isolates from P. bracteatum , P. glaucum, P. fugax , and P. argemone grown in the Kurdistan Province, west of Iran, of which 13 isolates were from roots, three from capsules and one from stems. To study secondary metabolite profiles of endophytic fungi for producing morphinan alkaloids, 6 strains (BR4, BR6, GR1, GR4, PR1 and PS1) with more differences in morphological features were selected. Screening of fungal extracts for morphinan alkaloids The extracts of all selected strains under the same condition were screened by HPLC to detect fungal morphinan compounds. The results showed that the peak positions and shapes of the selected fungi closely matched those of the chemical references for morphine, demonstrating that all the distinct fungi produced morphine. Among the examined isolates, the highest yield of morphine (21.33 mg/g) and codeine (2.03 mg/g) was detected in BR6 whereas BR4 and PS1 contained lower yield of morphine (2.76 mg/g) and (0.18 mg/g), respectively. The GR1 extract contained morphine only (Table 3). Based on these results, BR6 was identified as the best strain to produce morphinan. By GC/MS confirmation of BR6 as a morphinan producing endophytic fungus, authentic papaverine and morphine yielded at 22.222 and 22.090 Retention Time (min) respectively. Also, this analysis indicated that BR6 produced 30 volatile compounds which were identified and described by their molecular structures, functions, and the time of leaching identified by peaks (Table 4). Among several detected alkaloids papaverine has the highest percentage. In addition to alkaloids, some compounds were detected in BR6 extract, most produced by Papaver species and other plants as secondary metabolites. For example, heptadecane, epi-bicyclosesquiphellandrene, delta-Cadinene naphthalene, ethofumesate, 2-ethylacridine, 4H-pyrane-3-carboxamide, ethidimuron, and hexadecanoic acid are some plants metabolites with antibacterial, anticancer, pesticide, herbicide, and antioxidant efficacy which were produced by BR6 (Table 4). These results can confirm the remarkable similarity between the endophytic fungi and P. bracteatum in terms of producing secondary metabolites 33–37 . Characterization of selected morphinan producing fungus The best morphinan producing fungal isolate (BR6) selected to study in more details was deposited in the culture collection of the Iranian Research Institute of Plant Protection, IRAN, Tehran, Iran (IRAN 4653C) and the Centraalbureau voor Schimmelcultures, CBS, Utrecht, The Netherlands (CBS 149789). The identity of the selected isolate IRAN 4653C studied based on multi-gene phylogenetic analyses and morological features. Phylogenetic analysis Megablast search of NCBIs GenBank nucleotide database, with the ITS and TUB sequences gave closest hits to Pithoascus intermedius CBS 217.32 (ITS: 99.6%, 494/498, GenBank NR_132953; TUB: 94.2%, 455/483, 2 gaps, GenBank LM652662) and Pithoascus nidicola CBS 197.61 (95%, 511/538, 12 gaps, GenBank MH858021; TUB: 95.7%, 429/448, 1 gap, GenBank LM65266 3 ), and using TEF1-α sequence the closest hits were Pithoascus intermedius CBS 217.32 (96.6%, 926/959, 2 gaps, GenBank LM6525 79 ) and Pithoascus stoveri CBS 197.61 (97.5%, 935/959, 2 gaps, GenBank LM652581). Sequences of our isolate IRAN 4653C were aligned with available authentic sequences of Microascaceae members (ITS: 37, TEF1-α: 28, TUB2: 29 sequences) and Trichoderma asperellum NBRC 101777 as outgroup retrieved from GenBank. Alignments for the ITS, TEF1-α, and TUB2 sequences including gaps contained 709, 976 and 601 characters, respectively. Single gene phylogenies confirmed the same phylogenetic position for our isolate and placed it within the genus Pithoascus (Figs S1–S3). The combined alignment of three loci including gaps contained 2288 characters, of which 164 were variable and parsimony uninformative, and 1375 were unvariable. Following a heuristic search of the remaining 749 parsimony informative characters, four trees with the same overall topology and the lowest parsimonious steps (CI = 0.47, HI = 0.53, RI = 0.64) were found. The best nucleotide substitution model for all three loci (ITS, TEF1-α, TUB2) is the general time-reversible model of evolution (Rodríguez et al., 1990) according to MrModelTest. This model assumes a discrete gamma distribution (GTR+I+G) with six rate categories (lsetnst = 6, rates = invgamma), dirichlet (1,1,1,1) base frequencies, and includes estimation of invariable sites. 194 trees were removed as burn-in from the 782 trees that were produced by the Bayesian analysis of the concatenated alignments of three loci. The remaining 588 trees were used to calculate the consensus tree and posterior probability values (PP). By the end of the run, the average standard deviation of split frequencies was 0.009567. The Bayesian tree with similar topology as the trees resulting from MP analysis is shown in Figure 2-4. Using bootstrap support values at the nodes and BI/MP posterior probabilities, the MP tree was mapped onto a Baysian tree. In both MP and BI analyses our isolate IRAN 4653C clustered in Pithoascus genus separated from all known species in a well-supported clade close to P. intermedius , P. exsertus and P. nidicola . Based on nucleotide sequences of examined three loci our isolate is differed from all three closely related species P. intermedius (ITS: 2 substitutions, 2 deletions/insertions; TEF1-α: 33 substitutions; TUB2: 33 substitutions, 1 deletion/insertion), P. exsertus (ITS: 35 substitutions; 21 deletions/insertions; TEF1-α: 38 substitutions, 1 deletion/insertion; TUB2: 43 substitutions; 4 deletions/insertions) and P. nidicola (ITS: 27 substitutions, 5 deletions/insertions; TEF1-α: 38 substitutions; TUB2: 25 substitutions, 1 deletion/insertion) and distinguished as a new species for science and named here as Pithoascus kurdistanensis sp. nov. Taxonomy and nomenclature Pithoascus kurdistanensis Mohammadi S., Bahramnejad B. & Abdollahz. sp. nov. Fig. 2 MycoBank MB849386 Etymology. Name refers to Kurdistan Province, Iran, where this species was first found. Description. Ascomata unpapillate, globose, pale to dark brown or black, semi-immersed or superficial, scattered or aggregated in dense crusts, covered with aerial hyphae, non-ostiolate, (67–) 80–120 (–243) µm, with a pseudoparenchymatous, layered, dark, thick-walled peridium. Setae aseptate or septate, straight or flexsuous, unbranched, pale to dark brown, (8–) 18–25 (–40) × 2–4 µm. Asci hyaline, globose, evanescent, 8-spored, (5–) 5.5–7.7 (–10) µm (av. ± S.D. = 6.9 ± 1.5). Ascospores conglobate inside the ascus, forming globose to sub-globose, small to large compact masses when asci disintegrate, hyaline at first, buff to olivaceous buff when mature, yellowish brown in mass, thin-walled, aseptate, navicular or lunate, often plano-convex, germ pores indistinct, (4.8–) 5.3–5.7 (–6.1) × (1.6–) 1.9–2.2 (–2.5) µm (av. ± S.D. = 5.5 ± 0.3 × 2 ± 0.2 µm). Conidiophores absent. Conidiogenous cells hyaline, cylindrical to ampulliform, rarely reduced to short swollen supporting cells, annellidic, smooth, rarely roughened and thin-walled, born singly, often laterally and rarely apically on aerial hyphae, (6–) 21–16 (–19) × (1.3–) 1.5–1.7 (–2.9) µm (av. ± S.D. = 13.2 ± 3.8 × 1.7 ± 0.4 µm). Conidia globose to pyriform, with a truncate base, smooth and thin-walled, aseptate, arranged in long basipetal dry chains, (3.3–) 3.5–5 (–5.7) × (2.8–) 3.5–4 (–4.5) µm (av. ± S.D. = 4.2 ± 0.7 × 3.6 ± 0.4 µm). Culture characteristics. Colonies with appressed and immersed hyphae and aerial mycelium in the middle, whitish to pale grey. Colonies with daily rate less than 1 mm reaching 12, 10 and 10 mm diam on MEA, OA and PDA after 14 d at room temperature 20–25 °C. Typus. IRAN, Kurdistan Province, Divandarreh, Saral region (35°33'57"N 46°48'47"E), Papaver bracteatum , 06 May 2018, H. Maroufi (holotype IRAN 18259F; ex-type strain IRAN 4653C = CBS 149789). Notes. In multi-gene phylogeny, Pithoascus kurdistanensis placed close to P. intermedius , P. exsertus and P. nidicola in a clade distinct from all introduced species (Fig. 1). It is also distinguished from all other species in single-gene phylogenies based on ITS, TEF-1α , and TUB2 sequences (Figs. S1-S3). Asexual morph in P. exsertus and P. lunatus and sexual morph in P. ater have not been reported. While most Pithoascus species ( P. intermedius , P. nidicola , P. stoveri , P. ater ) with known asexual morph produce solitary conidia on conidiogenous cells, Pithoascus kurdistanensis and P. persica produce conidia in long dry chains. Moreover, P. kurdistanensis is differentiated from closely related species P. intermedius , P. nidicola and P. exsertus by having smaller conidia, shorter ascospores and larger ascomata and ascospores, respectively (Table 5). This species is also separated from all described species by having setae, shape and size of asci (Table 5). Thus far, no setae have been reported in Pithoascus species. Main morphological characters useful for discriminating Pithoascus species are provided in table 5. Discussion Endophytes often generate secondary metabolites that resemble those of their host plants. Because of this, they represent a very promising source of new bioactive compounds with a variety of possible biological uses 38 . A few studies have investigated endophytic microorganisms of Papaver species 39,40 . 2 bacterial endophytes that were recently isolated from various P. somniferum parts were studied for their capacity to increase resistance to a downy mildew 40 . Moreover, an endophytic fungus isolated from P . somniferum showed potential antimicrobial activities against four human bacterial pathogens and two fungi 41 . By confirmation of morphinan alkaloids presence in P. glaucum , P. fugax , P. argemone , and P. bracteatum , this study has been performed to investigate secondary metabolite profiles of associated endophytic fungi. There is the first report concerning the production of morphinan from endophytic fungi. HPLC results indicating the most potent endophytic fungal isolate in alkaloids production is IRAN 4653C which, isolated from the most efficient species of Papaver ( P. bracteatum ) in terms of producing morphine. Thus, it can be some similarities between endophytic fungus and its host. To further confirm, the IRAN 4653C production of morphinan was subjected to GC-MS high resolution analysis 42,43 , in which addition to morphinan alkaloids, some plant metabolites are detected. Most of these compounds possess various biological activities, including antiviral, antimicrobial, anticancer, and antioxidant properties 33–35 . In terms of morphology, strain IRAN 4653C were related to genera of the Microascaceae . Various studies have been done to determine the best molecular markers for phylogenetic relationships of Microascaceae 20 . At the first step to clarify the identity of our isolate IRAN 4653C, we sequenced the internal transcribed spacer (ITS) region as a well-known universal DNA barcode marker in fungal phylogeny. BLAST analyses of ITS sequence data revealed that IRAN 4653C is closely related with Pithoascus species. The ITS, EF1-a, and TUB genes were the three loci sequenced in this study, which was conducted in response to a thorough investigation by Sandoval-Denis et al. 30 . Phylogenetic analyses of Pithoascus species were optimized using this multi-gene approach. Based on multigene phylogenetic analyses strain IRAN 4653C placed in the genus Pithoascus distinct from all described species (i.e., P. ater , P. exsertus , P. intermedious , P. lunatu , P. nidicola , P. persica , and P. stoveri ) and introduced here as a new species named Pithoascus kurdistanensis sp. nov. Main morphological characters useful in discrimination of Pithoascus species were determined and used to compare and discriminate strain IRAN 4653. Despite the overlap in morphological features, we can use a set of sexual/asexual morph characters together with phylogenetic analyses of sequence data to discriminate Pithoascus species. The most important character we documented in P. kurdistanesis is producing conidial chain in asexual morph as it is observed in morphology of P. persica which is not reported for Pithoascus species with asexual morph 29–31 . Moreover, we have seen setae in P. kurdistanicus for the first time in Pithoascus species. Thus, as the number of species and studied isolates around the world are growing, we will get clearer and roubust definition from the genus Pithoascus and species boundaries which contribute to revise the descriptions in future. Microbial synthesis overcomes many of the obstacles complicated by using compounds produced in plants 44 . Thus, P. kurdistanesis IRAN 4653C could be an attractive alternative to plants for production alkaloids. Also, there is excellent potential in using P. kurdistanesis as a model system to investigate the new BIA biosynthesis pathways as a valuable source for the pharmaceutical industry. Additional studies addressing the completed genome sequence of the P. kurdistanesis and BIA biosynthetic pathway in this fungus will provide. Materials and Methods Sampling and fungal isolation During April to May 2018, 4 different Papaver species; P. bracteatum , P. glaucum , P. fugax , and P. argemone were collected at flowering growth stage from different origins in Kurdistan Province, west of Iran. Disease-free plant samples were surface sterilized and plated on Potato Dextrose Agar (PDA) with 100 mg/L ampicillin and streptomycin. Plates were incubated at 25 ˚C and monitored every day for growth of endophytic colonies and absence of saprophytic contamination. Following single-spore purification, the colonies were kept on PDA between 4 and 8 °C. Preparation of endophytic fungl extracts Five (9 mm diameter) agar plugs of fungal isolates were inoculated in 500 mL flasks containing 200 mL of Potato Dextrose Broth (PDB) in the dark at 30 ˚C for 21 days on a rotary shaker (120 rpm). Then, flasks were kept in the dark at 25 ˚C under static conditions and fermented for 7 days. Methanol (MeOH) and chloroform (20:80 mL), two distinct solvents, were used for the extraction process in order to obtain both extracellular and intracellular secondary metabolites. 4 weeks later, the mycelia was removed from the culture by filtering it through 2 layers of cheesecloth. Each culture broth was given the same amount of organic solvent (1:1) to extract extracellular metabolites using this method. To remove waxy materials, the extract was placed at 4 ˚C for 12 hours. After gathering the organic phase, the solvent was extracted using a vacuum rotary evaporator set at 45°C. A final concentration of 250 mg/mL was achieved by dissolving the weighed residue in double distilled water. Lastly, a membrane with a 0.22 μm pore size was used to filter the concentrated extracts, which were then utilized in further experiments. The mycelial biomass was harvested, washed thoroughly, and were macerated in 2X volume of solvents for 2 days on a rotary shaker. Next, a thorough homogenization of the mycelia was performed. The extracellular metabolites in the supernatants were further treated as previously explained. Before being utilized in bioassays, the secondary metabolites from every sample were kept at -20 ˚C. Analysis of extraction alkaloids by HPLC The Papaver purified alkaloids were provided by Darou Pakhsh company, Tehran, Iran. For preparing the stock solution of standards, 1 mg was solved in MeOH. The alkaloid solution concentration series were made to calibrate the curves (morphine: 7.8–125.0 μg/ml; codeine: 7.8–125.0 μg/ml; thebaine 7.8–250.0 μg/ml; papaverine 7.8–250 μg/ml). The solution of plant samples and fungi samples were prepared and filtered with 0.45 μm diameter and transferred into HPLC vials and kept at the -20 ˚C until injection. An HPLC system with a C18 column (particle size 5 μm, 4 mm X 150 mm) and a Photo Diode Array Detector (PDA) was used to perform the HPLC analysis. The gradient mobile phase was solvent A (water) and B (acetonitrile) both of which contain 0.1% formic acid. The process of separation started with A and went from 100:0 to 85:15 in 20 minutes. It then reached 80:20 in 30 minutes, 65:35 in 40 minutes, and 100 B after a 10-minute column flush with 100% B. 280 nm was the wavelength used for detection. Every sample received two injections. The calibration curves for the standards were then made by plotting the peak areas against the concentrations. Gas chromatography-mass spectrometry (GC-MS) The selected endophytic fungus extracts presumed to contain high amounts of morphinan compounds were analysed with gas chromatography/mass spectrometry (GC/MS) for validation. The fungus extract (0.5 mg) was transferred into a vial then added 1 of mL methanol and hydrochloric. The vial was vortexed and left at 50 ˚C for 12 hours and analyzed by GC-MS 45 . A 5977E MSD operating in EI mode at 70 eV was connected to an Agilent Technologies 7820A gas chromatograph, which was used to analyze 1 µl of the sample. The setup included a 30 m x 0.25 mm fused-silica capillary column with a stationary phase of 0.25 µm HP-5MS (Agilent Technologies, UK). The injection temperature was set at 270 ˚C and helium was used as the carrier gas at a constant flow rate of 1 ml/min. The temperature was then increased at a rate of 10 ˚C/min to 320 ˚C and held for 1 minute. For the analysis of polar compounds, a temperature program was used consisting of 2 minutes of isothermal heating at 70 ˚C, followed by a 10 ˚C/min ramp to 320 ˚C, and a final 2 minutes at 320 ˚C. Impact mass spectra were recorded at 70 eV, and all spectra were recorded in the mass range of 50 to 800 m/z. DNA extraction, amplification and sequencing Using the DenaZist Asia fungal DNA isolation kit, total genomic DNA was extracted from fungal mycelia. To identify the selected fungus at the species level, ITS, TEF-1α, and TUB2 gene regions were amplified. All PCR reactions were performed using TopTaq PCR Master Mix kit to to ensure precise amplification in a total reaction volume of 25 µl. The PCR conditions consisted of an initial denaturation step at 94 ˚C for 5 minutes, followed by 30 cycles of 94 ˚C for 30 seconds, 58 ˚C for 20 seconds, and 72 ˚C for 30 seconds, with a final extension step of 72 ˚C for 10 minutes. The PCR products were then purified and sequenced by Marcon Co. (South Korea). A summary of all primers used in this study can be found in Table 1. Phylogenetic analyses The authentic sequences from GenBank (http://www.ncbi.nlm.nih.gov) were added to the novel sequences produced in this study (Table 2), and MAFFT v. 7 (http://mafft.cbrc.jp/alignment/server/index.html) was used to align the sequences. When needed, alignment was adjusted by hand in BioEdit v. 7.0. After independently aligning each locus, Mesquite 2.75 was used to concatenate the alignments 46 . Phylogenetic analyses of single and combined alignments (ITS, TEF1-α, and TUB2), were carried out using Maximum Parsimony (MP) and Bayesian Inference (BI) algorithms. For MP analysis using PAUP v. 4.0b10 (Swofford, 2003) we followed Abdollahzadeh et al. (2013) 47,48 . MrModelTest v. 2.3 was used to identify the best nucleotide substitution models for every locus (Nylander, 2004) 49 . BI was conducted via the CIPRES Science Gateway portal (https://www.phylo.org/; Miller et al., 2012) using MrBayes v. 3.2.6 (Huelsenbeck & Ronquist 2001, Ronquist & Huelsenbeck 2003) as described by Nahvi Moghadam et al. (2022) 50–53 . FigTree v. 1.4.3 (http://tree.bio.ed.ac.uk/software/figtree) was used to show phylogenetic trees, while Adobe Illustrator CS2 v. 12.0.0 was used for editing. Taxonomic innovations have been added to MycoBank (www.MycoBank.org; Crous et al., 2004). Morphological characterization Cultural characteristics were recorded on MEA, OA and PDA at room temperature (20–25 °C). Cultures were kept under mixed near-UV and cool-white fluorescent lights with a 12 -hour light-dark cycle for three to four months to promote both sexual and asexual reproductions. Microscopy and measurements based on at least 20 fungal structures were done using an Olympus BX51 microscope equipped with a Cell Sense Entry measurement module and an Olympus DP72 camera according to Nahvi Moghadam et al. (2022) 53 Declarations Funding The University of Kurdistan, Sanandaj, Iran. The Canadian Institute for Health, Canada funded R. C. Levesque for this research. Author Contribution Project management was done by B. B, R.C.L. and A. V.. Samples were prepared and gathered by S.M. Data generation and analysis were done by S.M., J.A., and S.B. Manuscript draft prepared by S.M. The work was examined and edited by all authors. The completed manuscript was read and approved by the authors. Acknowledgments The authors would like to thank Dr. Jeff Gauthier for his knowledge and assistance. All processes related to plant collection for this research were carried out by Hossein Maroofi, a botanist at the Kurdistan Agricultural and Natural Resources Research and Education Center. Data Availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.• All data generated or analysed during this study are included in this published article [and its supplementary information files]. Verification and documentation of all collected plants, along with their storage under specific herbarium codes, can be accessed through this link (Herbarium Details | Kurdistan Agricultural and Natural Resources Research and Education Center (nybg.org). The herbarium code assigned to the collected Papaver bracteatum is 8931. As per the regulations governing the collection of wild plants in Iran, permission was not required. However, authors comply with the IUCN Policy Statement on Research Involving Species at Risk of Extinction and the Convention on the Trade in Endangered Species of Wild Fauna and Flora. The plant collection serves as a valuable resource for botanical research, offering access to a diverse range of plant species for scientific study. Researchers can explore various fields including plant taxonomy, genetics, physiology, ecology, and other branches of botanical science, utilizing the resources provided by the collection. Additionally, regarding the results, all findings are accessible, and we are more than willing to share them upon request. All data generated or analysed during this study are included in this published article and its supplementary information files. References Roberts, M. F., Kutchan, T. M., Brown, R. T. & Coscia, C. J. 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The CIPRES science gateway: Enabling high-impact science for phylogenetics researchers with limited resources. in ACM International Conference Proceeding Series (2012). doi:10.1145/2335755.2335836. Huelsenbeck, J. P. & Ronquist, F. MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 17 , (2001). Ronquist, F. & Huelsenbeck, J. P. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19 , (2003). Moghadam, J. N., Khaledi, E., Abdollahzadeh, J. & Amini, J. Seimatosporium marivanicum, Sporocadus kurdistanicus, and Xenoseimatosporium kurdistanicum: three new pestalotioid species associated with grapevine trunk diseases from the Kurdistan Province, Iran. Mycol Prog 21 , (2022). Tables Table 1 . Primers are used for PCR amplification and sequencing. Gene Primer Product size [bp] Ta ̊C Designation Nucleotide sequence ITS ITS1 5'-CTTGGTCATTTAGAGGAAGTAA-3' 1500 53 ITS4 5'-TCCTCCGCTTATTGATATGC-3' TUB BT2a 5'-GGTAACCAAATCGGTGCTGCTTTC-3' 550 55 BT2b 5'-ACCCTCAGTGTAGTGACCCTTGGC-3' EF 983F 5'-GCy 1 CCy 1 GGhCAy 1 CGTGAy 1 TTy 1 AT-3' 1000 65 2218R 5'-ATGACACCr 1 ACr 1 GCr 1 ACr 1 GTy 1 TG-3' 1 Degenerate nucleotides: y, C or T; h, A, C, or T; r, A or G. Table 2. Strains used in phylogenetic analyses. Species Isolate No.1 Host Location GenBank accession number2 ITS TUB2 EF1-α Pithoascus kurdistanensis IRAN 4653C T Papaver bracteatum Iran OR224479 OR215044 OR221070 Pithoascus intermedius CBS 217.32T Root of Fragaria vesca USA LM652450 LM652662 LM652579 Pithoascus nidicola CBS 197.61T Dipodomys merriami USA LM652451 LM652663 LM652580 Pithoascus exsertus CBS 819.70T Megachile willoughbiella Denmark LM652449 LM652578 LM652661 Pithoascus ater CBS 400.34T Unknown Unknown LM652447 LM652659 LM652576 Pithoascus lunatus CBS 103.85T Skin ( Tinea plantari s) Germany LN850784 LN850881 LN850929 Pithoascus stoveri CBS 176.71T Root of Beta vulgaris USA LM652453 LM652664 LM652581 Pithoascus persica IRAN 3309C Root of Ferula ovina Iran MF186873 - MK430530 Wardomycopsis inopinata FMR 10305 Soil Myanmar LM652498 LN851160 LN851106 Pseudoscopulariopsis schumacheri CBS 435.86T soil Spain LM652455 LM652666 LM652583 Microascus longirostris CBS 196.61NT Wasp’s nest USA LM652421 LM652634 LM652566 Microascus croci CBS 296.61T Air Brazil LM652408 LM652622 LM652561 Microascus gracilis CBS 369.70T Food Japan LM652412 LM652625 HG380390 Scopulariopsis cordiae CBS 138129T Human finger USA LM652491 LM652673 HG380422 Wardomycopsis humicola CBS 487.66T Soil Canada LM652497 LN851157 LN851103 Scopulariopsis brevicaulis UTHSC 07-1812 Human toenail USA LM652470 LM652677 HG380366 Gamsia aggregata CBS 251.69T Dung of carnivore USA LM652378 LN851144 LN851090 Lophotrichus macrosporus NBRC 32894* Sheep dung Iraq 3289401* - - Lophotrichus plumbescens NBRC 30864T* Soil Thailand 03086401* - - Kernia nitida CBS 282.52 Chrysolina sanguinolenta France MH857035 MN982415 MN982407 Kernia pachypleura CBS 776.70 Soil of paddy field Japan MH859937 MN982417 MN982410 Scedosporium aurantiacum CBS 116910 Ulcer of ankle Spain HQ231818 - - Scedosporium boydii CBS 330.93 Bronchial secretion Netherlands AY863196 - - Petriella sordida CBS 124169 Corner of a bathroom Netherlands GQ426957 - - Petriellopsis africana CBS 311.72T Brown sandy soil Namibia AJ888425 - - Trichoderma asperellum NBRC 101777T* sclerotia of Sclerotinia minor USA 11776302* - - Petriella setifera CBS. 391.75 infection of dolphin Netherlands AY882344 - Microascus murinus CBS 830.70T Composed municipal waste Germany LM652424 LM652637 HG380404 Yunnania carbonaria CBS 205.61T Soil Panama LM652489 LM652695 HG380385 Fairmania singularis CBS 414.64 Laboratory contaminant Japan LM652442 LN851088 LN851142 Cephalotrichum asperulum CBS 127.22 Seed Netherlands LN850959 LN851113 LN851060 Gamsia columbina CBS 546.69T Milled Oryza sativa Japan LM652379 LN851148 LN851094 Acaulium acremonium MUCL 8274 Wheat field soil Germany LM652457 LN851109 LN851056 Acaulium acremonium MUCL 8409 Soil Germany LM652458 LN851110 LN851057 Acaulium acremonium CBS 290.38T Skin of a horse Denmark LM652456 LN851108 HG380362 Cephalotrichum cylindricum CBS 448.51 Timber South Africa LN850964 LN851118 LN851065 Wardomyces inflatus CBS 216.61T Wood, Acer sp. Canada LM652496 LN851152 LN851098 Parascedosporium tectonae CBS 127.84T Seed Jamaica AY228113 - EF151409 Wardomyces giganteus CBS 746.69T Insect frass in dead log Canada LM652411 LN851150 LN851096 1CBS Culture collection of the Westerdijk Fungal Biodiversity Institute, Utrecht, The Netherlands; FMR: Facultat de Medicina i Ciències de la Salut, Reus, Spain; FMR: Facultat de Medicina i Ciències de la Salut, Reus, Spain; NBRC: National Biological Resource Centre, Japan; UAMH: University of Alberta Microfungus Collection and Herbarium, Canada; UTHSC: Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center, San Antonio, USA 2ITS: Internal transcribed spacer of the rDNA and 5.8S regions; EF-1α: partial translation elongation factor gene; TUB2: partial beta-tubulin gene. * Sequences obtained from the NBRC database. Table 3 . HPLC analysis for the presence of the morphinan alkaloids in fungi isolates (Mg/g). Fungi isolates Morphine Codeine Papaverine Thebaine BR4 2.76 0.16 -- -- BR6 23.06 2.03 -- -- GR1 9.12 -- -- -- GR4 13.81 0.38 -- -- PR1 4.26 0.18 -- -- PS1 5.73 0.49 -- -- Tables 4 . GC-MS analysis revealed the presence of bioactive compounds in the BR6. S. No Name of the compound Ret time Identified Compound Details Molecular Formula 1 Dibutyl phthalate 24.508 Organic compound, ester compound, plasticizer C16H22O4 2 Bis(2-ethylhexyl) phthalate 24.508 Organic compound, phthalates, plasticizer in medical devices C24H38O4 3 3-OXO-18-NOR-ENT-ROS-4-ENE-15. beta.,16 Acetonide 24.508 Organic compound, Antifeedent, antiviral C22H34O3 4 1,2-Benzenedicarboxylic acid, 3-phenoxy 24.508 Organic compound, ester compound, plasticizer C14H10O5 5 Ethofumesate 24.110 Organic compound, ester, and a member of 1-benzofurans. ester and a member of 1-benzofurans. herbicide. C13H18O5S 6 Benzylideneacetone 24.508 Organic compound, ketone, flavoring ingredient in food and perfumes, C10H10O 7 2-Ethylacridine 24.110 Organic compound, Antimicrobial and antitumor, antioxidant activity C15H13N 8 4H-Pyrane-3-carboxamide 24.110 Organic compound, heterocyclic compounds, pharmacological activities, such as spasmolytic, diuretic, anticoagulant, anticancer, and anti anaphylactic activity C6H6O3 9 1,3-dimethyl-4-azaphenanthrene 24.110 Organic compound, Polycyclic aromatic hydrocarbons, potent toxic environmental pollutants with carcinogenic properties C15H13N 10 Codeine 23.565 Organic compound, plant alkaloids, opiate and prodrug of morphine used to treat pain, coughing, and diarrhea C18H21NO3 11 Morphinan-6-ol, 7,8-didehydro-4,5-epoxy-17-methyl-3-(phenylmethoxy)-, (5alpha,6alpha)- 23.565 Organic compound, plant alkaloids, opiate analgesic psychoactive drug C24H25NO3 12 Papaverine 22.09 Organic compound, opium alkaloid, an antispasmodic drug C20H21NO4 13 Ethidimuron 22.222 Organic Chemicals, Methylurea Compounds, herbicide, and pesticide C7H12N4O3S2 14 Hexadecanoic acid 18.796 Organic compound, fatty acid found in animals, plants, and microorganisms, food additive, and emollient or surfactant in cosmetics. C16H32O2 15 Pentadecanoic acid 18.796 Organic compound, a saturated fatty acid, has a role as a plant metabolite, a food component, a Daphnia Magna metabolite, a human blood serum metabolite, and an algal metabolite C15H30O2 16 Vamidothion 18.796 Organic compound, organic thiophosphate, insecticide and acaricide C8H18NO4PS2 17 Dimethoate 18.796 Organic compound. monocarboxylic acid amide, insecticide, and on several field-grown agricultural crops C5H12NO3PS2 18 Demephion 18.796 Organic compound, organothiophosphate, insecticide C10H26O6P2S4 19 Octadecane 17.478 organic compound, alkane hydrocarbon, used as a solvent, lubricant, transformer oil, and anti-corrosion agents C18H38 20 Eicosane 16.391 Organic compound, alkane, use in the petrochemical industry C20H42 21 Trimethylsilyl [2-(4-chlorophenyl)-4-phenyl-1,3-thiazol-5-yl]acetate 16.727 Unknown 22 Trimethylsilyl 3-methoxy-2-(2-oxo-2-((trimethylsilyl)oxy)ethoxy)benzoate 16.727 Organic compound, No activity reported C16H26O6Si2 23 Hexasiloxane, tetradecamethyl 16.727 Organic compound, No activity reported C14H42O5Si6 24 Heptadecane 16.391 Organic compound, an alkane hydrocarbon, role as a plant metabolite and a volatile oil component CH₃(CH₂)₁₅CH₃ 25 Eicosane 16.391 Organic compound, an alkane, used in cosmetics, lubricants, plasticizers, and in the petrochemical industry. C20H42 26 Bicyclo[4.4.0]dec-1-ene, 2-isopropyl-5-methyl-9-methylene- 15.263 Organic compound, No activity reported C15H24 27 isoledene 15.263 Organic compound, No activity reported C15H24 28 delta.-Cadinene Naphthalene 15.923 Organic compound, essential oils, antibacterial C15H24 28 Epi-bicyclosesquiphellandrene 15.765 Organic compound, sesquiterpenoids, antimicrobial C15H24 30 Gamma-Cadinene 15.849 Organic compound, essential oils, sesquiterpenoids, antibacterial C15H24 Table 5 . Main morphological features for discriminating Pithoascus species. Species Conidia Ascospores size (µm) Asci Ascocarps Reference size (µm) arrangement size (µm) shape size (µm) ostiole P. ater 4–9 × 4.5–8.5 Solitary Nr* Nr* Nr* Nr* Nr* Sandoval-Denis et al., 2016 P. exsertus Nr* Nr* 6.7–12 × 1.3–2.5 10–18.5 × 4–7.5 cylindrical to barrel 213–438 + Skou 1973 P. intermedius 4–8 × 4.5–7.5 Solitary 5–6 × 2–2.5 11–15 × 7–9 ellipsoid/clavate 120–200 + Doveri 2011 P. kurdistanensis 3.3–5.7 × 2.8–4.5 Chain 4.8–6.1 × 1.6–2.5 5–10 globose 67–243 - This study P. lunatus Nr* Nr* 5–5.5 × 2.5 9.5–12.5 × 5–9 subglobose to ellipsoid 111–143 + Jagielski et al., 2016 P. nidicola 4–5 × 2.5–3.5 Solitary 6–8 × 2–2.5 10–15 × 7–12 ellipsoid to barrel 90–160 + von Arx 1973; Sandoval-Denis et al., 2016 P. persica 4–5 Chain 6.5–8 × 3.5–3.8 Nr* Nr* 200–260 - Tazik et al. 2020 P. stoveri 5–8 × 3–4 Solitary 6–7.5 × 2–3 11–15 × 7–10 ellipsoid to barrel 50–110 - von Arx 1973; Sandoval-Denis et al., 2016 *: Not reported Additional Declarations No competing interests reported. Supplementary Files FigS1ITS.pdf FigS2TEF.pdf FigS3TUB.pdf Cite Share Download PDF Status: Published Journal Publication published 30 Sep, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 20 May, 2024 Reviews received at journal 19 May, 2024 Reviews received at journal 09 May, 2024 Reviewers agreed at journal 01 May, 2024 Reviewers agreed at journal 30 Apr, 2024 Reviewers invited by journal 29 Apr, 2024 Editor assigned by journal 29 Apr, 2024 Editor invited by journal 29 Apr, 2024 Submission checks completed at journal 29 Apr, 2024 First submitted to journal 05 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Levesque","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIie3RMWvCQBTA8RducHmtawS1X+FKBgfBz5JDaNeOQkOaEtBFcNVvYRGcX3iQW9K9o9AvEDe7lF5i7dSLjg73h3Ac5MdL7gBcrqtMJPXSFghk1q55PGom3pF00iPBanMZkVS/fAEZzLLXT5zEvY2+ybIDMLaX4x1BNLKSbqHSAAsOtnwbMhrifzxIgnxsJb7vTTurKakto2QwBAqS5CWiicy+Vt+x2qQo6w+7K3RpyEvjFNgnQq0FVidgZul5NYXtBFXqlzkHy/pf5CPe6/kThbm2kxZnZRjFvcXinfeHybDf59bbroyereTU6XZ+t+FZ8EdcLpfL9U8/e3BX54TdxhIAAAAASUVORK5CYII=","orcid":"","institution":"Université Laval Québec","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Roger","middleName":"C.","lastName":"Levesque","suffix":""}],"badges":[],"createdAt":"2024-03-05 18:37:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4018361/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4018361/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-71344-z","type":"published","date":"2024-09-30T15:57:38+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55922817,"identity":"480c21af-36f6-4d15-8895-b7c82fd2cd48","added_by":"auto","created_at":"2024-05-06 10:39:04","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":656244,"visible":true,"origin":"","legend":"\u003cp\u003eBayesian analysis of a concatenated alignment of ITS, TEF-1α, and TUB2 yielded the phylogenetic tree. At each node, the maximum parsimony bootstrap support values (MP) and Bayesian posterior probabilities (PP) are displayed (PP/MP). Ex-type strains are indicated with T. The scale bar represents the expected number of changes per site. The tree was rooted to \u003cem\u003eTrichoderma asperellum\u003c/em\u003e (NBRC 101777).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4018361/v1/2e2792de4d75ba5cf0d7f3cc.jpeg"},{"id":55922457,"identity":"0069b3dc-0c90-49db-aed8-99fe57a1328d","added_by":"auto","created_at":"2024-05-06 10:31:04","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":935620,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003ePithoascus kurdistanensis\u003c/em\u003e: (a–c) colonies on PDA (4-wk-old), MEA (2-wk-old) and OA (2-wk-old); (d, e) conidial long basipetal chain on conidiogenous cells; (f) hyaline, aseptate conidia; (g) immature ascomata; (h) mature ascomata with setae; (i) round compact masses of ascospores outside asci; (j) globose 8-spored asci; (k, l) mature ascospores. Scale bars: d–f, j–l = 5 μm; g–i = 10 μm.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4018361/v1/f31835b59b70f5f760b78d9a.jpeg"},{"id":66097624,"identity":"4f36853d-f0c5-4105-b463-542010c04ded","added_by":"auto","created_at":"2024-10-07 16:14:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2647090,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4018361/v1/9669db1b-3b88-4a44-aa6c-e41e50520b1e.pdf"},{"id":55922455,"identity":"1590a13c-681d-454d-9735-666f041b4619","added_by":"auto","created_at":"2024-05-06 10:31:04","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":247589,"visible":true,"origin":"","legend":"","description":"","filename":"FigS1ITS.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4018361/v1/f9af458114ed8d53b99840f5.pdf"},{"id":55922459,"identity":"7141fc4b-0926-4f98-8015-e6c13ff34b0f","added_by":"auto","created_at":"2024-05-06 10:31:04","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":236064,"visible":true,"origin":"","legend":"","description":"","filename":"FigS2TEF.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4018361/v1/7c23e20aceb4a2701a7dc52e.pdf"},{"id":55922818,"identity":"c1078c04-64b1-4135-8515-0fed80bd824b","added_by":"auto","created_at":"2024-05-06 10:39:04","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":258962,"visible":true,"origin":"","legend":"","description":"","filename":"FigS3TUB.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4018361/v1/9fb246a184b50eee1187bd51.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pithoascus kurdistanensis: Discovery of a Novel Endophytic Fungal Species Associated with Papaver bracteatum, and its Production of Morphine Compounds","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBenzylisoquinoline alkaloids (BIAs) are a group of specialized metabolites found in plants of the order Ranunculales, specifically in families like \u003cem\u003ePapaveraceae\u003c/em\u003e. These compounds contain nitrogen and have various biological activities \u003csup\u003e1\u003c/sup\u003e. As secondary metabolites, BIAs are not crucial for normal growth and development, but they do play a crucial role in protecting plants against herbivores and pathogens. \u003csup\u003e2\u003c/sup\u003e. Tyrosine as a precursor of BIAs exhibits a wide range of pharmacological activities\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003csup\u003e3\u003c/sup\u003e. One subclass of benzylisoquinoline alkaloids is morphinan alkaloids, which are potent analgesics that have been used for thousands of years. These alkaloids are exclusively produced in plants of the \u003cem\u003ePapaver\u003c/em\u003e genus. \u003csup\u003e4\u003c/sup\u003e. The \u003cem\u003ePapaver\u003c/em\u003e genus is renowned for its production of various BIAs, including the potent painkiller morphine, the cough suppressant codeine, the muscle relaxant papaverine, an intermediate used in the semi-synthesis of other pentacyclic morphinan-based drugs, and the anti-microbial compound sanguinarine \u003csup\u003e5\u003c/sup\u003e. Nowadays, morphine and codeine continue to be the most beneficial and efficient compounds in medicine worldwide\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003csup\u003e6\u003c/sup\u003e. The\u0026nbsp;intricate structures of morphinan,\u0026nbsp;with five chiral centers,\u0026nbsp;highlight the\u0026nbsp;uneconomic\u0026nbsp;commercial synthesis and cultivation of poppy as\u0026nbsp;the most effective method\u0026nbsp;for\u0026nbsp;producing\u0026nbsp;opiate analgesics\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003csup\u003e7\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePapaver\u003c/em\u003e as a genus (commonly known as poppy) belongs to the \u003cem\u003ePapaveraceae\u003c/em\u003e family containing 830 species. These species are primarily found in temperate regions of the Northern Hemisphere, South Africa, and southern America \u003csup\u003e8\u003c/sup\u003e. Cullen (1966) reported 26 species of \u003cem\u003ePapaver\u003c/em\u003e, including 5 that were endemic to Iran. However, this report did not take into account the sectional classification of the genus. More recent reports have identified species of this genus in various floristic regions of Iran \u003csup\u003e9,10\u003c/sup\u003e \u003cem\u003ePapaver\u003c/em\u003e species can produce more than 170 different alkaloids, mainly in the form of benzylisoquinoline alkaloids (BIAs).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEndophytes constitute any kind of organism that colonizes healthy plant tissue intercellularly and/or intracellularly, apparently without causing visible damage or morphological changes \u003csup\u003e11\u003c/sup\u003e. It is known that endophytic fungi live inside their host plant for protracted periods of time; the earliest records of them date back 400 million years. \u003csup\u003e12\u003c/sup\u003e. Endophytic fungi are a valuable and reputable source of bioactive and novel compounds with immense potential in the fields of medicine and agriculture. They also play a crucial role in enhancing the ecological adaptability of their host plants \u003csup\u003e13,14\u003c/sup\u003e. Interactions between plants and fungi can increase the production of bioactive metabolites in medicinal plants \u003csup\u003e15\u003c/sup\u003e. Also, some specified endophytic fungi mimic the host plant\u0026apos;s secondary metabolites profile and tend to produce the plant medicinal products \u003csup\u003e16,17\u003c/sup\u003e such as taxol, camptothecin, and its structural analogs \u003csup\u003e18\u003c/sup\u003e, ginkgolide \u003csup\u003e19\u003c/sup\u003e. Therefore, researchers focusing on the isolation of endophytic fungi from pharmaceutical plants can discover many undescribed endophytic fungi species. Many of these fungi possess the ability to produce a diverse range of secondary metabolites that are associated with plants, exhibiting a wide array of biological activities.\u003c/p\u003e\n\u003cp\u003eEndophytic fungi are frequently found within their host\u0026apos;s metabolic networks, leading to changes in metabolite production and an increase in the presence of active compounds in medicinal plants \u003csup\u003e20\u003c/sup\u003e The evaluation of endophytic fungi plays a significant role in the production of bioactive metabolites which allows them to effectively adapt to their host and perform certain functions like synthesizing chemical compounds within these plants \u003csup\u003e21\u003c/sup\u003e. Researchers believe that the reason why endophytes produce certain chemical compounds is that genetic recombination occurred during evolution between the endophyte and its host \u003csup\u003e22,23\u003c/sup\u003e. This is the theory that was originally presented as an explanation for why the endophytic fungus \u003cem\u003eTaxomyces andreanae\u003c/em\u003e should produce taxol \u003csup\u003e24\u003c/sup\u003e. Endophytic fungi in comparison with plants, grow much faster and are more appropriate for metabolic engineering \u003csup\u003e25\u003c/sup\u003e. Also, easier metabolites extraction from fungi could be valuable from both ecological and economic standpoints \u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eDuring a study on endophytic fungi associated with \u003cem\u003ePapaver\u003c/em\u003e species and their secondary metabolite profiles for morphine alkaloids, we found a morphinan producing endophytic fungus placed in \u003cem\u003ePithoascus\u003c/em\u003e genus based on phylogenetic analyses of three loci (ITS, TEF-1\u0026alpha;, TUB2) sequence data and morphological features.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePithoascus\u003c/em\u003e was established by Von Arx (1973) based on the type species \u003cem\u003eP. nidicola\u003c/em\u003e, which formerly included in \u003cem\u003eMicroascus\u003c/em\u003e\u003csup\u003e26\u003c/sup\u003e. Some researchers based on morphology considered this genus as a synonym with \u003cem\u003eMicroascus\u003c/em\u003e but reinstated by Sandoval-Dennis et al. (2016) \u003csup\u003e27\u0026ndash;30\u003c/sup\u003e based on a multi-gene (LSU, ITS, TEF-1\u0026alpha;, TUB2) phylogenetic study. \u003cem\u003ePithoascus\u003c/em\u003e is a member of the Microascaceae family and is distinguished by ascomata with simple or barely noticeable ostioles and navicular to fusiform ascospores devoid of germ pores. Asexual morph produced in some species with single and laterally annellidic conidiogenous cells and globose to pyriform 1-celled solitary conidia \u003csup\u003e30\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccording to Indexfungorum (June 2023; www.indexfungorum.org) and Mycobank (www.mycobank.org) nine species have been introduced in \u003cem\u003ePithoascus\u003c/em\u003e. These species are associated with humans (hair, nail, tinea plantaris), rat (\u003cem\u003eDipodomys merriami\u003c/em\u003e), wasps (\u003cem\u003eMegachile willughbiella, Osmia rufa\u003c/em\u003e), soil and plants (e.g. \u003cem\u003eBeta\u003c/em\u003e \u003cem\u003evulgaris\u003c/em\u003e, \u003cem\u003eFragaria\u003c/em\u003e \u003cem\u003evesca\u003c/em\u003e, \u003cem\u003eFerula ovina\u003c/em\u003e) as saprophyte, endophyte and potential pathogen \u003csup\u003e30\u0026ndash;32\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHere we introduce an endophytic fungus within \u003cem\u003ePithoascus\u003c/em\u003e genus as a new species and a taxonomic novelty for science which is able to produce morphinan species. This finding\u0026nbsp;indicates the importance of microbial community associated with \u003cem\u003ePapaver\u003c/em\u003e species as microbial potential sources to discover and produce new and valuable secondary metabolites.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cul\u003e\n \u003cli\u003eIsolation of fungi\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWe collected 17 endophytic fungal isolates from \u003cem\u003eP. bracteatum\u003c/em\u003e, \u003cem\u003eP. glaucum,\u003c/em\u003e \u003cem\u003eP. fugax\u003c/em\u003e, and \u003cem\u003eP. argemone\u003c/em\u003e grown in the Kurdistan Province, west of Iran, of which 13 isolates were from roots, three from capsules and one from stems. To study secondary metabolite profiles of endophytic fungi for producing morphinan alkaloids, 6\u0026nbsp;strains (BR4, BR6, GR1, GR4, PR1 and PS1) with more differences in morphological features were selected.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eScreening of fungal extracts for morphinan alkaloids\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe extracts of all selected strains under the same condition were screened by HPLC to detect fungal morphinan compounds.\u0026nbsp;The results showed that the peak positions and shapes of the selected fungi closely matched those of the chemical references for morphine, demonstrating that all the distinct fungi produced morphine.\u003c/p\u003e\n\u003cp\u003eAmong the examined isolates, the highest yield of morphine (21.33\u0026nbsp;mg/g) and codeine (2.03\u0026nbsp;mg/g) was detected in BR6 whereas BR4 and PS1 contained lower yield of morphine (2.76\u0026nbsp;mg/g) and (0.18\u0026nbsp;mg/g), respectively. The GR1 extract contained morphine only (Table 3).\u0026nbsp;Based on these results,\u0026nbsp;BR6 was identified as the best strain to produce morphinan.\u003c/p\u003e\n\u003cp\u003eBy GC/MS confirmation of BR6 as a morphinan producing endophytic fungus, authentic papaverine and morphine yielded at 22.222 and 22.090 Retention Time (min) respectively.\u0026nbsp;Also, this analysis indicated\u0026nbsp;that BR6 produced 30 volatile compounds which were identified and described by their molecular structures, functions, and the time of leaching identified by peaks (Table 4). Among several detected alkaloids papaverine has the highest percentage.\u003c/p\u003e\n\u003cp\u003eIn addition to alkaloids, some compounds were detected in BR6 extract, most produced by Papaver species and other plants as secondary metabolites. For example, heptadecane, epi-bicyclosesquiphellandrene, delta-Cadinene naphthalene, ethofumesate, 2-ethylacridine, 4H-pyrane-3-carboxamide, ethidimuron, and hexadecanoic acid are some plants metabolites with antibacterial, anticancer, pesticide, herbicide, and antioxidant efficacy which were produced by BR6 (Table 4). These results can confirm the remarkable similarity between the endophytic fungi and\u0026nbsp;\u003cem\u003eP. bracteatum\u0026nbsp;\u003c/em\u003ein terms of producing secondary metabolites\u0026nbsp;\u003csup\u003e33\u0026ndash;37\u003c/sup\u003e\u003cem\u003e.\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eCharacterization of selected morphinan producing fungus\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe best morphinan producing fungal isolate (BR6) selected to study in more details was deposited in the culture collection of the Iranian Research Institute of Plant Protection, IRAN, Tehran, Iran (IRAN 4653C) and the Centraalbureau voor Schimmelcultures, CBS, Utrecht, The Netherlands (CBS 149789). The identity of the selected isolate IRAN 4653C studied based on multi-gene phylogenetic analyses and morological features.\u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePhylogenetic analysis\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eMegablast search of NCBIs GenBank nucleotide database, with the ITS and TUB sequences gave closest hits to \u003cem\u003ePithoascus\u003c/em\u003e \u003cem\u003eintermedius\u003c/em\u003e CBS 217.32 (ITS: 99.6%, 494/498, GenBank NR_132953; TUB: 94.2%, 455/483, 2 gaps, GenBank LM652662) and \u003cem\u003ePithoascus\u003c/em\u003e \u003cem\u003enidicola\u003c/em\u003e CBS 197.61 (95%, 511/538, 12 gaps, GenBank MH858021; TUB: 95.7%, 429/448, 1 gap, GenBank LM65266\u003cu\u003e3\u003c/u\u003e), and using TEF1-\u0026alpha; sequence the closest hits were \u003cem\u003ePithoascus\u003c/em\u003e \u003cem\u003eintermedius\u003c/em\u003e CBS 217.32 (96.6%, 926/959, 2 gaps, GenBank LM6525\u003cu\u003e79\u003c/u\u003e) and \u003cem\u003ePithoascus\u003c/em\u003e \u003cem\u003estoveri\u003c/em\u003e CBS 197.61 (97.5%, 935/959, 2 gaps, GenBank LM652581).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSequences of our isolate IRAN 4653C were aligned with available authentic sequences of \u003cem\u003eMicroascaceae\u003c/em\u003e members (ITS: 37, TEF1-\u0026alpha;: 28, TUB2: 29 sequences) and \u003cem\u003eTrichoderma asperellum\u0026nbsp;\u003c/em\u003eNBRC 101777 as outgroup retrieved from GenBank. Alignments for the ITS, TEF1-\u0026alpha;, and TUB2 sequences including gaps contained 709, 976 and 601 characters, respectively. Single gene phylogenies confirmed the same phylogenetic position for our isolate and placed it within the genus \u003cem\u003ePithoascus\u003c/em\u003e (Figs S1\u0026ndash;S3). The combined alignment of three loci including gaps contained 2288 characters, of which 164 were variable and parsimony uninformative, and 1375 were unvariable. Following a heuristic search of the remaining 749 parsimony informative characters, four trees with the same overall topology and the lowest parsimonious steps (CI = 0.47, HI = 0.53, RI = 0.64) were found.\u003c/p\u003e\n\u003cp\u003eThe best nucleotide substitution model for all three loci (ITS, TEF1-\u0026alpha;, TUB2) is the general time-reversible model of evolution (Rodr\u0026iacute;guez et al., 1990) according to MrModelTest. This model assumes a discrete gamma distribution (GTR+I+G) with six rate categories (lsetnst = 6, rates = invgamma), dirichlet (1,1,1,1) base frequencies, and includes estimation of invariable sites. 194 trees were removed as burn-in from the 782 trees that were produced by the Bayesian analysis of the concatenated alignments of three loci. The remaining 588 trees were used to calculate the consensus tree and posterior probability values (PP). By the end of the run, the average standard deviation of split frequencies was\u0026nbsp;0.009567. The Bayesian tree with similar topology as the trees resulting from MP analysis is shown in Figure 2-4. Using bootstrap support values at the nodes and BI/MP posterior probabilities, the MP tree was mapped onto a Baysian tree. In both MP and BI analyses our isolate IRAN 4653C clustered in \u003cem\u003ePithoascus\u003c/em\u003e genus separated from all known species in a well-supported clade close to \u003cem\u003eP. intermedius\u003c/em\u003e, \u003cem\u003eP. exsertus\u003c/em\u003e and \u003cem\u003eP. nidicola\u003c/em\u003e. Based on nucleotide sequences of examined three loci our isolate is differed from all three closely related species \u003cem\u003eP. intermedius\u003c/em\u003e (ITS: 2 substitutions, 2 deletions/insertions; TEF1-\u0026alpha;: 33 substitutions; TUB2: 33 substitutions, 1 deletion/insertion), \u003cem\u003eP. exsertus\u003c/em\u003e (ITS: 35 substitutions; 21 deletions/insertions; TEF1-\u0026alpha;: 38 substitutions, 1 deletion/insertion; TUB2: 43 substitutions; 4 deletions/insertions) and \u003cem\u003eP. nidicola\u003c/em\u003e (ITS: 27 substitutions, 5 deletions/insertions; TEF1-\u0026alpha;: 38 substitutions; TUB2: 25 substitutions, 1 deletion/insertion) and distinguished as a new species for science and named here as \u003cem\u003ePithoascus kurdistanensis\u003c/em\u003e sp. nov.\u003c/p\u003e\n\u003cp\u003eTaxonomy and nomenclature\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePithoascus kurdistanensis\u003c/em\u003e\u003c/strong\u003e Mohammadi S., Bahramnejad B. \u0026amp; Abdollahz. \u003cstrong\u003esp. nov.\u0026nbsp;\u003c/strong\u003eFig. 2\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMycoBank\u0026nbsp;\u003c/strong\u003eMB849386\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEtymology.\u003c/strong\u003e Name refers to Kurdistan Province, Iran, where this species was first found.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDescription.\u003c/strong\u003e Ascomata unpapillate, globose, pale to dark brown or black, semi-immersed or superficial, scattered or aggregated in dense crusts, covered with aerial hyphae, non-ostiolate, (67\u0026ndash;) 80\u0026ndash;120 (\u0026ndash;243) \u0026micro;m, with a pseudoparenchymatous, layered, dark, thick-walled peridium. Setae aseptate or septate, straight or flexsuous, unbranched, pale to dark brown, (8\u0026ndash;) 18\u0026ndash;25 (\u0026ndash;40) \u0026times; 2\u0026ndash;4 \u0026micro;m. Asci hyaline, globose, evanescent, 8-spored, (5\u0026ndash;) 5.5\u0026ndash;7.7 (\u0026ndash;10) \u0026micro;m (av. \u0026plusmn; S.D. = 6.9 \u0026plusmn; 1.5). Ascospores conglobate inside the ascus, forming globose to sub-globose, small to large compact masses when asci disintegrate, hyaline at first, buff to olivaceous buff when mature, yellowish brown in mass, thin-walled, aseptate, navicular or lunate, often plano-convex, germ pores indistinct, (4.8\u0026ndash;) 5.3\u0026ndash;5.7 (\u0026ndash;6.1) \u0026times; (1.6\u0026ndash;) 1.9\u0026ndash;2.2 (\u0026ndash;2.5) \u0026micro;m (av. \u0026plusmn; S.D. = 5.5 \u0026plusmn; 0.3 \u0026times; 2 \u0026plusmn; 0.2 \u0026micro;m). Conidiophores absent. Conidiogenous cells hyaline, cylindrical to ampulliform, rarely reduced to short swollen supporting cells, annellidic, smooth, rarely roughened and thin-walled, born singly, often laterally and rarely apically on aerial hyphae, (6\u0026ndash;) 21\u0026ndash;16 (\u0026ndash;19) \u0026times; (1.3\u0026ndash;) 1.5\u0026ndash;1.7 (\u0026ndash;2.9) \u0026micro;m (av. \u0026plusmn; S.D. = 13.2 \u0026plusmn; 3.8 \u0026times; 1.7 \u0026plusmn; 0.4 \u0026micro;m). Conidia globose to pyriform, with a truncate base, smooth and thin-walled, aseptate, arranged in long basipetal dry chains, (3.3\u0026ndash;) 3.5\u0026ndash;5 (\u0026ndash;5.7) \u0026times; (2.8\u0026ndash;) 3.5\u0026ndash;4 (\u0026ndash;4.5) \u0026micro;m (av. \u0026plusmn; S.D. = 4.2 \u0026plusmn; 0.7 \u0026times; 3.6 \u0026plusmn; 0.4 \u0026micro;m).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCulture characteristics.\u0026nbsp;\u003c/strong\u003eColonies with appressed and immersed hyphae and aerial mycelium in the middle, whitish to pale grey. Colonies with daily rate less than 1 mm reaching 12, 10 and 10 mm diam on MEA, OA and PDA after 14 d at room temperature 20\u0026ndash;25 \u0026deg;C.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTypus.\u003c/strong\u003e IRAN, Kurdistan Province, Divandarreh, Saral region (35\u0026deg;33\u0026apos;57\u0026quot;N 46\u0026deg;48\u0026apos;47\u0026quot;E), \u003cem\u003ePapaver\u003c/em\u003e \u003cem\u003ebracteatum\u003c/em\u003e, 06 May 2018, H. Maroufi (holotype IRAN 18259F; ex-type strain IRAN 4653C = CBS 149789).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNotes.\u0026nbsp;\u003c/strong\u003eIn multi-gene phylogeny,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003ePithoascus\u003c/em\u003e \u003cem\u003ekurdistanensis\u003c/em\u003e placed close to \u003cem\u003eP. intermedius\u003c/em\u003e, \u003cem\u003eP. exsertus\u003c/em\u003e and \u003cem\u003eP. nidicola\u003c/em\u003e in a clade distinct from all introduced species (Fig. 1). It is also distinguished from all other species in single-gene phylogenies based on ITS, \u003cem\u003eTEF-1\u0026alpha;\u003c/em\u003e, and \u003cem\u003eTUB2\u003c/em\u003e sequences (Figs. S1-S3). Asexual morph in \u003cem\u003eP. exsertus\u003c/em\u003e and \u003cem\u003eP. lunatus\u003c/em\u003e and sexual morph in \u003cem\u003eP. ater\u003c/em\u003e have not been reported. While most \u003cem\u003ePithoascus\u003c/em\u003e species (\u003cem\u003eP. intermedius\u003c/em\u003e, \u003cem\u003eP. nidicola\u003c/em\u003e, \u003cem\u003eP. stoveri\u003c/em\u003e, \u003cem\u003eP. ater\u003c/em\u003e) with known asexual morph produce solitary conidia on conidiogenous cells, \u003cem\u003ePithoascus\u003c/em\u003e \u003cem\u003ekurdistanensis\u003c/em\u003e and \u003cem\u003eP. persica\u003c/em\u003e produce conidia in long dry chains. Moreover, \u003cem\u003eP. kurdistanensis\u003c/em\u003e is differentiated from closely related species \u003cem\u003eP. intermedius\u003c/em\u003e, \u003cem\u003eP. nidicola\u003c/em\u003e and \u003cem\u003eP. exsertus\u003c/em\u003e by having smaller conidia, shorter ascospores and larger ascomata and ascospores, respectively (Table 5). This species is also separated from all described species by having setae, shape and size of asci (Table 5). Thus far, no setae have been reported in \u003cem\u003ePithoascus\u003c/em\u003e species. Main morphological characters useful for discriminating \u003cem\u003ePithoascus\u003c/em\u003e species are provided in table 5.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEndophytes often generate secondary metabolites that resemble those of their host plants. Because of this, they represent a very promising source of new bioactive compounds with a variety of possible biological uses \u003csup\u003e38\u003c/sup\u003e. A few studies have investigated endophytic microorganisms of \u003cem\u003ePapaver\u003c/em\u003e species \u003csup\u003e39,40\u003c/sup\u003e. 2 bacterial endophytes that were recently isolated from various P. somniferum parts were studied for their capacity to increase resistance to a downy mildew \u003csup\u003e40\u003c/sup\u003e. Moreover, an endophytic fungus isolated from \u003cem\u003eP\u003c/em\u003e. \u003cem\u003esomniferum\u003c/em\u003e showed potential antimicrobial activities against four human bacterial pathogens and two fungi \u003csup\u003e41\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBy confirmation of morphinan alkaloids presence in \u003cem\u003eP. glaucum\u003c/em\u003e, \u003cem\u003eP. fugax\u003c/em\u003e, \u003cem\u003eP. argemone\u003c/em\u003e, and \u003cem\u003eP. bracteatum\u003c/em\u003e, this study has been performed to investigate secondary metabolite profiles of associated endophytic fungi. There is the first report concerning the production of morphinan from endophytic fungi. HPLC results indicating the most potent endophytic fungal isolate in alkaloids production is IRAN 4653C which, isolated from the most efficient species of \u003cem\u003ePapaver\u003c/em\u003e (\u003cem\u003eP. bracteatum\u003c/em\u003e) in terms of producing morphine. Thus, it can be some similarities between endophytic fungus and its host. To further confirm, the IRAN 4653C production of morphinan was subjected to GC-MS high resolution analysis \u003csup\u003e42,43\u003c/sup\u003e, in which addition to morphinan alkaloids, some plant metabolites are detected. Most of these compounds possess various biological activities, including antiviral, antimicrobial, anticancer, and antioxidant properties \u003csup\u003e33\u0026ndash;35\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn terms of morphology, strain IRAN 4653C were related to genera of the \u003cem\u003eMicroascaceae\u003c/em\u003e. Various studies have been done to determine the best molecular markers for phylogenetic relationships of \u003cem\u003eMicroascaceae\u003c/em\u003e \u003csup\u003e20\u003c/sup\u003e. At the first step to clarify the identity of our isolate IRAN 4653C, we sequenced the internal transcribed spacer (ITS) region as a well-known universal DNA barcode marker in fungal phylogeny. BLAST analyses of ITS sequence data revealed that IRAN 4653C is closely related with \u003cem\u003ePithoascus\u003c/em\u003e species. The ITS, EF1-a, and TUB genes were the three loci sequenced in this study, which was conducted in response to a thorough investigation by Sandoval-Denis et al.\u003csup\u003e30\u003c/sup\u003e. Phylogenetic analyses of \u003cem\u003ePithoascus\u003c/em\u003e species were optimized using this multi-gene approach.\u003c/p\u003e \u003cp\u003eBased on multigene phylogenetic analyses strain IRAN 4653C placed in the genus \u003cem\u003ePithoascus\u003c/em\u003e distinct from all described species (i.e., \u003cem\u003eP. ater\u003c/em\u003e, \u003cem\u003eP. exsertus\u003c/em\u003e, \u003cem\u003eP. intermedious\u003c/em\u003e, \u003cem\u003eP. lunatu\u003c/em\u003e, \u003cem\u003eP. nidicola\u003c/em\u003e, \u003cem\u003eP. persica\u003c/em\u003e, and \u003cem\u003eP. stoveri\u003c/em\u003e) and introduced here as a new species named \u003cem\u003ePithoascus kurdistanensis\u003c/em\u003e sp. nov. Main morphological characters useful in discrimination of \u003cem\u003ePithoascus\u003c/em\u003e species were determined and used to compare and discriminate strain IRAN 4653. Despite the overlap in morphological features, we can use a set of sexual/asexual morph characters together with phylogenetic analyses of sequence data to discriminate \u003cem\u003ePithoascus\u003c/em\u003e species. The most important character we documented in \u003cem\u003eP. kurdistanesis\u003c/em\u003e is producing conidial chain in asexual morph as it is observed in morphology of \u003cem\u003eP. persica\u003c/em\u003e which is not reported for \u003cem\u003ePithoascus\u003c/em\u003e species with asexual morph \u003csup\u003e29\u0026ndash;31\u003c/sup\u003e. Moreover, we have seen setae in \u003cem\u003eP. kurdistanicus\u003c/em\u003e for the first time in \u003cem\u003ePithoascus\u003c/em\u003e species. Thus, as the number of species and studied isolates around the world are growing, we will get clearer and roubust definition from the genus \u003cem\u003ePithoascus\u003c/em\u003e and species boundaries which contribute to revise the descriptions in future.\u003c/p\u003e \u003cp\u003eMicrobial synthesis overcomes many of the obstacles complicated by using compounds produced in plants \u003csup\u003e44\u003c/sup\u003e. Thus, \u003cem\u003eP. kurdistanesis\u003c/em\u003e IRAN 4653C could be an attractive alternative to plants for production alkaloids. Also, there is excellent potential in using \u003cem\u003eP. kurdistanesis\u003c/em\u003e as a model system to investigate the new BIA biosynthesis pathways as a valuable source for the pharmaceutical industry. Additional studies addressing the completed genome sequence of the \u003cem\u003eP. kurdistanesis\u003c/em\u003e and BIA biosynthetic pathway in this fungus will provide.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cul\u003e\n\u003cli\u003eSampling and fungal isolation\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eDuring April to May 2018, 4 different \u003cem\u003ePapaver\u003c/em\u003e species; \u003cem\u003eP. bracteatum\u003c/em\u003e, \u003cem\u003eP. glaucum\u003c/em\u003e, \u003cem\u003eP. fugax\u003c/em\u003e, and \u003cem\u003eP. argemone\u003c/em\u003e were collected at flowering growth stage from different origins in Kurdistan Province, west of Iran. Disease-free plant samples were surface sterilized and plated on Potato Dextrose Agar (PDA) with 100 mg/L ampicillin and streptomycin. Plates were incubated at 25 ˚C and monitored every day for growth of endophytic colonies and absence of saprophytic contamination. Following single-spore purification, the colonies were kept on PDA between 4 and 8 \u0026deg;C.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003ePreparation of endophytic fungl extracts \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eFive (9\u0026thinsp;mm diameter) agar plugs of fungal isolates were inoculated in 500\u0026thinsp;mL flasks containing 200\u0026thinsp;mL of Potato Dextrose Broth (PDB) in the dark at 30\u0026thinsp;˚C for 21\u0026thinsp;days on a rotary shaker (120 rpm). Then, flasks were kept in the dark at 25\u0026thinsp;˚C under static conditions and fermented for 7\u0026thinsp;days. Methanol (MeOH) and chloroform (20:80 mL), two distinct solvents, were used for the extraction process in order to obtain both extracellular and intracellular secondary metabolites. 4 weeks later, the mycelia was removed from the culture by filtering it through 2 layers of cheesecloth. Each culture broth was given the same amount of organic solvent (1:1) to extract extracellular metabolites using this method. To remove waxy materials, the extract was placed at 4 ˚C for 12 hours. After gathering the organic phase, the solvent was extracted using a vacuum rotary evaporator set at 45\u0026deg;C. A final concentration of 250 mg/mL was achieved by dissolving the weighed residue in double distilled water. Lastly, a membrane with a 0.22 \u0026mu;m pore size was used to filter the concentrated extracts, which were then utilized in further experiments.\u003c/p\u003e\n\u003cp\u003eThe mycelial biomass was harvested, washed thoroughly, and were macerated in 2X volume of solvents for 2 days on a rotary shaker. Next, a thorough homogenization of the mycelia was performed. The extracellular metabolites in the supernatants were further treated as previously explained. Before being utilized in bioassays, the secondary metabolites from every sample were kept at -20 ˚C.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eAnalysis of extraction alkaloids by HPLC\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe \u003cem\u003ePapaver\u003c/em\u003e purified alkaloids were provided by Darou Pakhsh company, Tehran, Iran. For preparing the stock solution of standards, 1 mg was solved in MeOH. The alkaloid solution concentration series were made to calibrate the curves (morphine: 7.8\u0026ndash;125.0 \u0026mu;g/ml; codeine: 7.8\u0026ndash;125.0 \u0026mu;g/ml; thebaine 7.8\u0026ndash;250.0 \u0026mu;g/ml; papaverine 7.8\u0026ndash;250 \u0026mu;g/ml). The solution of plant samples and fungi samples were prepared and filtered with 0.45 \u0026mu;m diameter and transferred into HPLC vials and kept at the -20 ˚C until injection. An HPLC system with a C18 column (particle size 5 \u0026mu;m, 4 mm X 150 mm) and a Photo Diode Array Detector (PDA) was used to perform the HPLC analysis. The gradient mobile phase was solvent A (water) and B (acetonitrile) both of which contain 0.1% formic acid. The process of separation started with A and went from 100:0 to 85:15 in 20 minutes. It then reached 80:20 in 30 minutes, 65:35 in 40 minutes, and 100 B after a 10-minute column flush with 100% B. 280 nm was the wavelength used for detection. Every sample received two injections. The calibration curves for the standards were then made by plotting the peak areas against the concentrations.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eGas chromatography-mass spectrometry (GC-MS)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe selected endophytic fungus extracts presumed to contain high amounts of morphinan compounds were analysed with gas chromatography/mass spectrometry (GC/MS) for validation. The fungus extract (0.5 mg) was transferred into a vial then added 1 of mL methanol and hydrochloric. The vial was vortexed and left at 50 ˚C for 12 hours and analyzed by GC-MS \u003csup\u003e45\u003c/sup\u003e. A 5977E MSD operating in EI mode at 70 eV was connected to an Agilent Technologies 7820A gas chromatograph, which was used to analyze 1 \u0026micro;l of the sample. The setup included a 30 m x 0.25 mm fused-silica capillary column with a stationary phase of 0.25 \u0026micro;m HP-5MS (Agilent Technologies, UK). The injection temperature was set at 270 ˚C and helium was used as the carrier gas at a constant flow rate of 1 ml/min. The temperature was then increased at a rate of 10 ˚C/min to 320 ˚C and held for 1 minute. For the analysis of polar compounds, a temperature program was used consisting of 2 minutes of isothermal heating at 70 ˚C, followed by a 10 ˚C/min ramp to 320 ˚C, and a final 2 minutes at 320 ˚C. Impact mass spectra were recorded at 70 eV, and all spectra were recorded in the mass range of 50 to 800 m/z. \u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eDNA extraction, amplification and sequencing\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eUsing the DenaZist Asia fungal DNA isolation kit, total genomic DNA was extracted from fungal mycelia. To identify the selected fungus at the species level, ITS, TEF-1\u0026alpha;, and TUB2 gene regions were amplified. All PCR reactions were performed using TopTaq PCR Master Mix kit to to ensure precise amplification in a total reaction volume of 25 \u0026micro;l. The PCR conditions consisted of an initial denaturation step at 94 ˚C for 5 minutes, followed by 30 cycles of 94 ˚C for 30 seconds, 58 ˚C for 20 seconds, and 72 ˚C for 30 seconds, with a final extension step of 72 ˚C for 10 minutes. The PCR products were then purified and sequenced by Marcon Co. (South Korea). A summary of all primers used in this study can be found in Table 1.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003ePhylogenetic analyses\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe authentic sequences from GenBank (http://www.ncbi.nlm.nih.gov) were added to the novel sequences produced in this study (Table 2), and MAFFT v. 7 (http://mafft.cbrc.jp/alignment/server/index.html) was used to align the sequences. When needed, alignment was adjusted by hand in BioEdit v. 7.0. After independently aligning each locus, Mesquite 2.75 was used to concatenate the alignments\u003csup\u003e\u003cspan lang=\"EN-US\"\u003e46\u003c/span\u003e\u003c/sup\u003e. Phylogenetic analyses of single and combined alignments (ITS, TEF1-\u0026alpha;, and TUB2), were carried out using Maximum Parsimony (MP) and Bayesian Inference (BI) algorithms. For MP analysis using PAUP v. 4.0b10 (Swofford, 2003) we followed Abdollahzadeh et al. (2013) \u003csup\u003e47,48\u003c/sup\u003e. MrModelTest v. 2.3 was used to identify the best nucleotide substitution models for every locus (Nylander, 2004)\u003csup\u003e49\u003c/sup\u003e. BI was conducted via the CIPRES Science Gateway portal (https://www.phylo.org/; Miller et al., 2012) using MrBayes v. 3.2.6 (Huelsenbeck \u0026amp; Ronquist 2001, Ronquist \u0026amp; Huelsenbeck 2003) as described by Nahvi Moghadam et al. (2022) \u003csup\u003e\u003cspan lang=\"EN-US\"\u003e50\u0026ndash;53\u003c/span\u003e\u003c/sup\u003e. FigTree v. 1.4.3 (http://tree.bio.ed.ac.uk/software/figtree) was used to show phylogenetic trees, while Adobe Illustrator CS2 v. 12.0.0 was used for editing. Taxonomic innovations have been added to MycoBank (www.MycoBank.org; Crous et al., 2004).\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eMorphological characterization\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eCultural characteristics were recorded on MEA, OA and PDA at room temperature (20\u0026ndash;25 \u0026deg;C). Cultures were kept under mixed near-UV and cool-white fluorescent lights with a 12 -hour light-dark cycle for three to four months to promote both sexual and asexual reproductions. Microscopy and measurements based on at least 20 fungal structures were done using an Olympus BX51 microscope equipped with a Cell Sense Entry measurement module and an Olympus DP72 camera according to Nahvi Moghadam et al. (2022) \u003csup\u003e53\u003c/sup\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe University of Kurdistan, Sanandaj, Iran. The Canadian Institute for Health, Canada funded R. C. Levesque for this research.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eProject management was done by B. B, R.C.L. and A. V.. Samples were prepared and gathered by S.M. Data generation and analysis were done by S.M., J.A., and S.B. Manuscript draft prepared by S.M. The work was examined and edited by all authors. The completed manuscript was read and approved by the authors.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThe authors would like to thank Dr. Jeff Gauthier for his knowledge and assistance. All processes related to plant collection for this research were carried out by Hossein Maroofi, a botanist at the Kurdistan Agricultural and Natural Resources Research and Education Center.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u0026bull; All data generated or analysed during this study are included in this published article [and its supplementary information files].\u003c/p\u003e\n\u003cp\u003eVerification and documentation of all collected plants, along with their storage under specific herbarium codes, can be accessed through this link (Herbarium Details | Kurdistan Agricultural and Natural Resources Research and Education Center (nybg.org). The herbarium code assigned to the collected \u003cem\u003ePapaver bracteatum\u003c/em\u003e is 8931.\u003c/p\u003e\n\u003cp\u003eAs per the regulations governing the collection of wild plants in Iran, permission was not required. However, authors comply with the IUCN Policy Statement on Research Involving Species at Risk of Extinction and the Convention on the Trade in Endangered Species of Wild Fauna and Flora. The plant collection serves as a valuable resource for botanical research, offering access to a diverse range of plant species for scientific study. Researchers can explore various fields including plant taxonomy, genetics, physiology, ecology, and other branches of botanical science, utilizing the resources provided by the collection. Additionally, regarding the results, all findings are accessible, and we are more than willing to share them upon request.\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article and its supplementary information files.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRoberts, M. F., Kutchan, T. M., Brown, R. T. \u0026amp; Coscia, C. J. 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Primers are used for PCR amplification and sequencing.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"617\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eGene\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.559157212317666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.64991896272285%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.045380875202593%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eProduct size [bp]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Ta ̊C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.559157212317666%\" valign=\"bottom\"\u003e\n \u003cp\u003eDesignation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.64991896272285%\" valign=\"bottom\"\u003e\n \u003cp\u003eNucleotide sequence\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.045380875202593%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003eITS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.559157212317666%\" valign=\"bottom\"\u003e\n \u003cp\u003eITS1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.64991896272285%\" valign=\"bottom\"\u003e\n \u003cp\u003e5\u0026apos;-CTTGGTCATTTAGAGGAAGTAA-3\u0026apos;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.045380875202593%\" valign=\"bottom\"\u003e\n \u003cp\u003e1500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.559157212317666%\" valign=\"bottom\"\u003e\n \u003cp\u003eITS4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.64991896272285%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;5\u0026apos;-TCCTCCGCTTATTGATATGC-3\u0026apos;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.045380875202593%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003eTUB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.559157212317666%\" valign=\"bottom\"\u003e\n \u003cp\u003eBT2a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.64991896272285%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;5\u0026apos;-GGTAACCAAATCGGTGCTGCTTTC-3\u0026apos;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.045380875202593%\" valign=\"bottom\"\u003e\n \u003cp\u003e550\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.559157212317666%\" valign=\"bottom\"\u003e\n \u003cp\u003eBT2b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.64991896272285%\" valign=\"bottom\"\u003e\n \u003cp\u003e5\u0026apos;-ACCCTCAGTGTAGTGACCCTTGGC-3\u0026apos;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.045380875202593%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003eEF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.559157212317666%\" valign=\"bottom\"\u003e\n \u003cp\u003e983F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.64991896272285%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;5\u0026apos;-GCy\u003csup\u003e1\u003c/sup\u003eCCy\u003csup\u003e1\u003c/sup\u003eGGhCAy\u003csup\u003e1\u003c/sup\u003eCGTGAy\u003csup\u003e1\u003c/sup\u003eTTy\u003csup\u003e1\u003c/sup\u003eAT-3\u0026apos;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.045380875202593%\" valign=\"bottom\"\u003e\n \u003cp\u003e1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.559157212317666%\" valign=\"bottom\"\u003e\n \u003cp\u003e2218R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.64991896272285%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;5\u0026apos;-ATGACACCr\u003csup\u003e1\u003c/sup\u003eACr\u003csup\u003e1\u003c/sup\u003eGCr\u003csup\u003e1\u003c/sup\u003eACr\u003csup\u003e1\u003c/sup\u003eGTy\u003csup\u003e1\u003c/sup\u003eTG-3\u0026apos;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.045380875202593%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.372771474878444%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDegenerate nucleotides: y, C or T; h, A, C, or T; r, A or G. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eStrains used in phylogenetic analyses.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"101%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpecies\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIsolate No.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHost\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.08247422680412%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGenBank accession number2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.78723404255319%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.27659574468085%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eITS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTUB2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.27659574468085%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEF1-\u0026alpha;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ePithoascus kurdistanensis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003eIRAN 4653C T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ePapaver bracteatum\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eOR224479\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eOR215044\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eOR221070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ePithoascus intermedius\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003eCBS 217.32T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\" valign=\"top\"\u003e\n \u003cp\u003eRoot of \u003cem\u003eFragaria vesca\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652450\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652662\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652579\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ePithoascus nidicola\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003eCBS 197.61T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003e\u003cem\u003eDipodomys merriami\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652663\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652580\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003ePithoascus exsertus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 819.70T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003e\u003cem\u003eMegachile willoughbiella\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eDenmark\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652578\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652661\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003ePithoascus ater\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 400.34T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652447\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652659\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652576\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003ePithoascus lunatus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 103.85T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eSkin (\u003cem\u003eTinea plantari\u003c/em\u003es)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eGermany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLN850784\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLN850881\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLN850929\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003ePithoascus stoveri\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 176.71T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eRoot of \u003cem\u003eBeta vulgaris\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652453\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652664\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652581\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ePithoascus persica\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eIRAN 3309C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eRoot of \u003cem\u003eFerula ovina\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eMF186873\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eMK430530\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eWardomycopsis inopinata \u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eFMR 10305\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eSoil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eMyanmar\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652498\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLN851160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLN851106\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003ePseudoscopulariopsis schumacheri\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003e\u0026nbsp;CBS 435.86T\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003esoil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eSpain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652666\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652583\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eMicroascus longirostris\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 196.61NT\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eWasp\u0026rsquo;s nest\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652634\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652566\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eMicroascus croci\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 296.61T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eAir\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652408\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652622\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652561\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eMicroascus gracilis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 369.70T\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eFood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652412\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eHG380390\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eScopulariopsis cordiae\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 138129T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eHuman finger\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652491\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652673\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eHG380422\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eWardomycopsis humicola\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 487.66T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eSoil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLN851157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLN851103\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eScopulariopsis brevicaulis\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eUTHSC 07-1812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eHuman toenail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652470\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652677\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eHG380366\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eGamsia aggregata\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 251.69T\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eDung of carnivore\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652378\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eLN851144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLN851090\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eLophotrichus macrosporus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eNBRC 32894*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eSheep dung\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eIraq\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003e3289401*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eLophotrichus plumbescens\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eNBRC 30864T*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eSoil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eThailand\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003e03086401*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eKernia nitida\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 282.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003e\u003cem\u003eChrysolina sanguinolenta\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eMH857035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eMN982415\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eMN982407\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eKernia pachypleura\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 776.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eSoil of paddy field\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eMH859937\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eMN982417\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eMN982410\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eScedosporium aurantiacum\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 116910\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eUlcer of ankle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eSpain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eHQ231818\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eScedosporium boydii\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 330.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eBronchial secretion\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eNetherlands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eAY863196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003ePetriella sordida\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 124169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eCorner of a bathroom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eNetherlands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eGQ426957\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003ePetriellopsis africana\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 311.72T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eBrown sandy soil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eNamibia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eAJ888425\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eTrichoderma asperellum\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eNBRC 101777T*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003esclerotia of \u003cem\u003eSclerotinia minor\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003e11776302*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003ePetriella setifera\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS. 391.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003einfection of dolphin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eNetherlands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eAY882344\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\"\u003e\n \u003cp\u003e\u003cem\u003eMicroascus murinus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 830.70T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eComposed municipal waste\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eGermany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652424\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLM652637\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eHG380404\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eYunnania carbonaria\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003eCBS 205.61T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\" valign=\"top\"\u003e\n \u003cp\u003eSoil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003ePanama\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLM652489\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eLM652695\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eHG380385\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eFairmania singularis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003eCBS 414.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\" valign=\"top\"\u003e\n \u003cp\u003eLaboratory contaminant\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLM652442\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eLN851088\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLN851142\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eCephalotrichum asperulum\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003eCBS 127.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\" valign=\"top\"\u003e\n \u003cp\u003eSeed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eNetherlands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLN850959\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eLN851113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLN851060\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eGamsia columbina\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003eCBS 546.69T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\" valign=\"top\"\u003e\n \u003cp\u003eMilled \u003cem\u003eOryza sativa\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLM652379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eLN851148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLN851094\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAcaulium acremonium\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eMUCL 8274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eWheat field soil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eGermany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652457\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eLN851109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLN851056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAcaulium acremonium\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eMUCL 8409\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eSoil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eGermany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652458\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eLN851110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLN851057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAcaulium acremonium\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 290.38T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eSkin of a horse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eDenmark\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652456\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eLN851108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eHG380362\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eCephalotrichum cylindricum\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 448.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eTimber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eSouth Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLN850964\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003eLN851118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLN851065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eWardomyces inflatus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 216.61T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eWood, \u003cem\u003eAcer\u003c/em\u003e sp.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eLN851152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003eLN851098\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eParascedosporium tectonae\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 127.84T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eSeed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eJamaica\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eAY228113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eEF151409\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eWardomyces\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003egiganteus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003eCBS 746.69T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\"\u003e\n \u003cp\u003eInsect frass in dead log\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003eLM652411\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eLN851150\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;LN851096\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e1CBS Culture collection of the Westerdijk Fungal Biodiversity Institute, Utrecht, The Netherlands; FMR: Facultat de Medicina i Ci\u0026egrave;ncies de la Salut, Reus, Spain; FMR: Facultat de Medicina i Ci\u0026egrave;ncies de la Salut, Reus, Spain; NBRC: National Biological Resource Centre, Japan; UAMH: University of Alberta Microfungus Collection and Herbarium, Canada; UTHSC: Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center, San Antonio, USA\u003c/p\u003e\n\u003cp\u003e2ITS: Internal transcribed spacer of the rDNA and 5.8S regions; EF-1\u0026alpha;: partial translation elongation factor gene; TUB2: partial beta-tubulin gene. * Sequences obtained from the NBRC database.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e.\u0026nbsp;HPLC analysis for the presence of the morphinan alkaloids in fungi isolates (Mg/g).\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"649\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.53846153846154%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eFungi isolates\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eMorphine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eCodeine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003ePapaverine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eThebaine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.53846153846154%\" valign=\"bottom\"\u003e\n \u003cp\u003eBR4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e2.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.53846153846154%\" valign=\"bottom\"\u003e\n \u003cp\u003eBR6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e23.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"bottom\"\u003e\n \u003cp\u003e2.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.53846153846154%\" valign=\"bottom\"\u003e\n \u003cp\u003eGR1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e9.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.53846153846154%\" valign=\"bottom\"\u003e\n \u003cp\u003eGR4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e13.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.53846153846154%\" valign=\"bottom\"\u003e\n \u003cp\u003ePR1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e4.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.53846153846154%\" valign=\"bottom\"\u003e\n \u003cp\u003ePS1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e5.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.615384615384617%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"bottom\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTables 4\u003c/strong\u003e.\u0026nbsp;GC-MS analysis revealed the presence of bioactive compounds in the BR6.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eS. No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eName of the compound\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRet time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIdentified Compound Details\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMolecular\u003cbr\u003e\u0026nbsp;Formula\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eDibutyl phthalate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e24.508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, ester compound, plasticizer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC16H22O4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eBis(2-ethylhexyl) phthalate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e24.508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, phthalates, plasticizer in medical devices\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC24H38O4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003e3-OXO-18-NOR-ENT-ROS-4-ENE-15. beta.,16 Acetonide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e24.508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, Antifeedent, antiviral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC22H34O3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003e1,2-Benzenedicarboxylic acid, 3-phenoxy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e24.508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, ester compound, plasticizer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC14H10O5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eEthofumesate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e24.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, ester, and a member of 1-benzofurans. ester and a member of 1-benzofurans. herbicide.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC13H18O5S\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eBenzylideneacetone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e24.508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, ketone, flavoring ingredient in food and perfumes,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC10H10O\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003e2-Ethylacridine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e24.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, Antimicrobial and\u003cbr\u003e\u0026nbsp;antitumor, antioxidant activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC15H13N\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003e4H-Pyrane-3-carboxamide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e24.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, heterocyclic compounds, pharmacological activities, such as spasmolytic, diuretic, anticoagulant, anticancer, and anti anaphylactic activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC6H6O3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003e1,3-dimethyl-4-azaphenanthrene\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e24.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, Polycyclic aromatic hydrocarbons, potent toxic environmental\u003cbr\u003e\u0026nbsp;pollutants with carcinogenic properties\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC15H13N\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eCodeine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e23.565\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, plant alkaloids, opiate and prodrug of morphine used to treat pain, coughing, and diarrhea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC18H21NO3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eMorphinan-6-ol, 7,8-didehydro-4,5-epoxy-17-methyl-3-(phenylmethoxy)-, (5alpha,6alpha)-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e23.565\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, plant alkaloids, opiate analgesic psychoactive drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC24H25NO3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003ePapaverine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e22.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, opium alkaloid, an antispasmodic drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC20H21NO4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eEthidimuron\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e22.222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;Organic Chemicals, Methylurea Compounds, herbicide, and pesticide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003e\u003ca href=\"https://pubchem.ncbi.nlm.nih.gov/#query=C7H12N4O3S2\" title=\"Find all compounds that have this formula\"\u003eC7H12N4O3S2\u003c/a\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eHexadecanoic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e18.796\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, fatty acid found in animals, plants, and microorganisms, food additive, and emollient or surfactant in cosmetics.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC16H32O2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003ePentadecanoic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e18.796\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, a saturated fatty acid, has a role as a plant metabolite, a food component, a Daphnia Magna metabolite, a human blood serum metabolite, and an algal metabolite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC15H30O2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eVamidothion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e18.796\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, organic thiophosphate, insecticide and acaricide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC8H18NO4PS2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eDimethoate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e18.796\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound. monocarboxylic acid amide, insecticide, and on several field-grown agricultural crops\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC5H12NO3PS2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eDemephion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e18.796\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, organothiophosphate, insecticide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC10H26O6P2S4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eOctadecane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e17.478\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eorganic compound, alkane hydrocarbon, used as a solvent, lubricant, transformer oil, and anti-corrosion agents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC18H38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eEicosane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e16.391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, alkane, use in the petrochemical industry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC20H42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eTrimethylsilyl [2-(4-chlorophenyl)-4-phenyl-1,3-thiazol-5-yl]acetate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e16.727\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eTrimethylsilyl 3-methoxy-2-(2-oxo-2-((trimethylsilyl)oxy)ethoxy)benzoate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e16.727\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, No activity reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC16H26O6Si2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eHexasiloxane, tetradecamethyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e16.727\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, No activity reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC14H42O5Si6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eHeptadecane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e16.391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, an alkane hydrocarbon, role as a plant metabolite and a volatile oil component\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eCH₃(CH₂)₁₅CH₃\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eEicosane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e16.391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, an alkane, used in cosmetics, lubricants, plasticizers, and in the petrochemical industry.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC20H42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eBicyclo[4.4.0]dec-1-ene, 2-isopropyl-5-methyl-9-methylene-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e15.263\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, No activity reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC15H24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eisoledene\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e15.263\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, No activity reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC15H24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003edelta.-Cadinene Naphthalene\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e15.923\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, essential oils, antibacterial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC15H24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eEpi-bicyclosesquiphellandrene\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e15.765\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, sesquiterpenoids, antimicrobial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC15H24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.07643312101911%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.05095541401274%\" valign=\"top\"\u003e\n \u003cp\u003eGamma-Cadinene\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.509554140127388%\" valign=\"top\"\u003e\n \u003cp\u003e15.849\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.32484076433121%\" valign=\"top\"\u003e\n \u003cp\u003eOrganic compound, essential oils, sesquiterpenoids, antibacterial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.038216560509554%\" valign=\"top\"\u003e\n \u003cp\u003eC15H24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u003c/strong\u003e. Main morphological features for discriminating \u003cem\u003ePithoascus\u003c/em\u003e species.\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"109%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpecies\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eConidia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAscospores size\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;(\u0026micro;m)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAsci\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Ascocarps\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eReference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003esize (\u0026micro;m)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003earrangement\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003esize (\u0026micro;m)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eshape\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003esize (\u0026micro;m)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eostiole\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003eP. ater\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003e4\u0026ndash;9 \u0026times; 4.5\u0026ndash;8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eSolitary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eSandoval-Denis et al., 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003eP. exsertus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003e6.7\u0026ndash;12 \u0026times; 1.3\u0026ndash;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e10\u0026ndash;18.5 \u0026times; 4\u0026ndash;7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003ecylindrical to barrel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e213\u0026ndash;438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eSkou 1973\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003eP. intermedius\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003e4\u0026ndash;8 \u0026times; 4.5\u0026ndash;7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eSolitary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003e5\u0026ndash;6 \u0026times; 2\u0026ndash;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e11\u0026ndash;15 \u0026times; 7\u0026ndash;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eellipsoid/clavate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e120\u0026ndash;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eDoveri 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003eP. kurdistanensis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003e3.3\u0026ndash;5.7 \u0026times; 2.8\u0026ndash;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eChain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003e4.8\u0026ndash;6.1 \u0026times; 1.6\u0026ndash;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e5\u0026ndash;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eglobose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e67\u0026ndash;243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eThis study\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003eP. lunatus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003e5\u0026ndash;5.5 \u0026times; 2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e9.5\u0026ndash;12.5 \u0026times; 5\u0026ndash;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003esubglobose to ellipsoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e111\u0026ndash;143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eJagielski et al., 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003eP. nidicola\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003e4\u0026ndash;5 \u0026times; 2.5\u0026ndash;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eSolitary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003e6\u0026ndash;8 \u0026nbsp;\u0026times; 2\u0026ndash;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e10\u0026ndash;15 \u0026times; 7\u0026ndash;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eellipsoid to barrel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e90\u0026ndash;160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003evon Arx 1973; Sandoval-Denis et al., 2016\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003eP. persica\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003e4\u0026ndash;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eChain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003e6.5\u0026ndash;8 \u0026times; 3.5\u0026ndash;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eNr*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e200\u0026ndash;260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003eTazik et al. 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003eP. stoveri\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003e5\u0026ndash;8 \u0026times; 3\u0026ndash;4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eSolitary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\" valign=\"top\"\u003e\n \u003cp\u003e6\u0026ndash;7.5 \u0026times; 2\u0026ndash;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e11\u0026ndash;15 \u0026times; 7\u0026ndash;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eellipsoid to barrel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e50\u0026ndash;110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.404255319148938%\" valign=\"top\"\u003e\n \u003cp\u003evon Arx 1973; Sandoval-Denis et al., 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*: Not reported\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Microascaceae, Pithoascus, Papaver, Morphinan alkaloids, HPLC, GC/MS","lastPublishedDoi":"10.21203/rs.3.rs-4018361/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4018361/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cem\u003ePapaver\u003c/em\u003e genus, commonly known as popies, is a valuable source of alkaloids used in medicine, including papaverine, morphine, codeine, and thebaine. We isolated six endophytic fungal isolates producing morphinan alkaloids from four \u003cem\u003ePapaver\u003c/em\u003e species growing in Kurdistan Province, Iran. To do this, a 1:1 mixture of methanol and chloroform was used to extract fungal cultures. The contents of morphinan alkaloids in the extracts were subsequently determined using phase high-performance liquid chromatography (HPLC). Among the morphinan alkaloid-producing fungal isolates, IRAN 4653C had the highest yield giving 23.06 (Mg/g) morphine and 2.03 (Mg/g) codeine when grown in potato dextrose liquid medium. Moreover, the morphinan productivity of IRAN 4653C was further validated by gas chromatography-mass spectrometry (GC-MS). The identity of this isolate was examined and recognized as a new fungal species named as \u003cem\u003ePithoascus kurdistanesis\u003c/em\u003e sp. nov. based on multi-gene phylogenetic analyses of ITS, TEF-1α, and TUB2 sequence data and morphological features. The morphinan-producing endophytic fungus and the isolated \u003cem\u003ePithoascus\u003c/em\u003e species from \u003cem\u003ePapaver\u003c/em\u003e are being reported for the first time. Accordingly, this fungus shows promise as a new source of valuable compounds which is illustrated and introduced here as a new \u003cem\u003eMicroascaceae\u003c/em\u003e member belonging to \u003cem\u003ePithoascus\u003c/em\u003e from Kurdistan Province, Iran.\u003c/p\u003e","manuscriptTitle":"Pithoascus kurdistanensis: Discovery of a Novel Endophytic Fungal Species Associated with Papaver bracteatum, and its Production of Morphine Compounds","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-06 10:30:59","doi":"10.21203/rs.3.rs-4018361/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-21T00:57:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-19T19:34:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-10T03:41:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2173d196-b32a-4958-b72d-5c3244dfff78","date":"2024-05-01T14:04:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"cd3dcb93-e754-483f-aac4-d5e682d07336","date":"2024-04-30T16:09:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-29T13:09:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-29T13:07:05+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-04-29T13:04:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-29T13:02:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-03-05T18:34:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4428591e-06cc-46dd-8856-9e00810bc554","owner":[],"postedDate":"May 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":31513654,"name":"Biological sciences/Microbiology/Fungi/Fungal biology"},{"id":31513655,"name":"Biological sciences/Microbiology/Fungi/Fungal evolution"}],"tags":[],"updatedAt":"2024-10-07T16:10:56+00:00","versionOfRecord":{"articleIdentity":"rs-4018361","link":"https://doi.org/10.1038/s41598-024-71344-z","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-09-30 15:57:38","publishedOnDateReadable":"September 30th, 2024"},"versionCreatedAt":"2024-05-06 10:30:59","video":"","vorDoi":"10.1038/s41598-024-71344-z","vorDoiUrl":"https://doi.org/10.1038/s41598-024-71344-z","workflowStages":[]},"version":"v1","identity":"rs-4018361","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4018361","identity":"rs-4018361","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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