Global distribution of deep-sea natural products shows environmental and phylogenetic undersampling and potential for biodiscovery

Global distribution of deep-sea natural products shows environmental and phylogenetic undersampling and potential for biodiscovery | 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 Global distribution of deep-sea natural products shows environmental and phylogenetic undersampling and potential for biodiscovery Lucy Harris, Gagan Preet, Ria Desai, Ahlam Haj Hasan, Johanne Vad, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6984270/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Natural products from marine and terrestrial organisms provide an important resource for medicinal chemistry and drug discovery. Defined as occurring at depths greater than 200 m, most of the ocean, by area and volume, is comprised of deep-sea environments. These contrasting ecosystems exhibit a wide range of temperature, pressure, and environmental chemistry conditions that harbour high phylogenetic diversity. Here we analyse the global distribution of Marine Natural Products (MNPs) from deep-sea organisms, which reveals chronic undersampling of the deep ocean as a reservoir of structural novelty and diverse bioactivity. The sources of 2907 compounds and extracts, compiled from published records, show a sampling bias towards benthic and shallower deep-sea habitats, with relatively few from areas beyond national jurisdictions and a concentration of records along geomorphological features that have been the focus of marine scientific interest such as seamounts and hydrothermal vents. The phylogenetic distribution of deep-sea MNPs is dominated by non-metazoan sources (76% of records) and Ascomycota fungi in particular (55%). Polyketides are the most prevalent metabolites in deep-sea MNPs, and cytotoxic and antibacterial properties are the most commonly reported bioactivities. Our analyses highlight a need for systematic sampling and consistent data reporting to explore potential relationships between structural novelty, bioactivity, phylogeny and deep-sea environmental conditions, which could guide targeted biodiscovery in our planet's largest biome and enable better assessment of the benefits of protecting deep-sea biodiversity from human impacts. Biological sciences/Chemical biology/Natural products Biological sciences/Drug discovery Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMaterial.pdf Supplementary Material: Data Summary Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6984270","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":476971625,"identity":"4063c8bf-569a-424e-a881-75f60b3008b9","order_by":0,"name":"Lucy Harris","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIie3RsQrCMBCA4SuFuES7yUHBvEJKFiefJVJolyodC4LWpR1du/kKPkIkg0vdXaXgC7iLpZM4xIwO+ceDD+44AJfrD5sABQUFzj5mxEwIUE9BOxcAvj3xlVcVy9KeTK9K5wTTY304dzksGGAizSRcS91QXJ1a7YsG4qjERP0gGdcUe4IxCSn4EjAtLQjHlDUD2dkSiRJuA9E9sVpMYdTfIgTll6iiD2kkQZiJ5/i1Zaze3ztabFgwSriRfMV/fsXlcrlcNr0BPPY4BLM+F9wAAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0006-9756-5957","institution":"University of Southampton","correspondingAuthor":true,"prefix":"","firstName":"Lucy","middleName":"","lastName":"Harris","suffix":""},{"id":476971626,"identity":"5ec21c57-cd50-48c7-819c-2b05a117cae2","order_by":1,"name":"Gagan Preet","email":"","orcid":"","institution":"University of Aberdeen","correspondingAuthor":false,"prefix":"","firstName":"Gagan","middleName":"","lastName":"Preet","suffix":""},{"id":476971627,"identity":"9f5117ee-0b27-4357-bf03-081aa63e4761","order_by":2,"name":"Ria Desai","email":"","orcid":"","institution":"University of Aberdeen","correspondingAuthor":false,"prefix":"","firstName":"Ria","middleName":"","lastName":"Desai","suffix":""},{"id":476971628,"identity":"10aa91bf-62eb-465a-a23d-3dd61aad8110","order_by":3,"name":"Ahlam Haj Hasan","email":"","orcid":"","institution":"Jordan University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Ahlam","middleName":"Haj","lastName":"Hasan","suffix":""},{"id":476971629,"identity":"87557f1d-8d51-47ae-aa63-e002d07d0884","order_by":4,"name":"Johanne Vad","email":"","orcid":"","institution":"University of Edinburgh","correspondingAuthor":false,"prefix":"","firstName":"Johanne","middleName":"","lastName":"Vad","suffix":""},{"id":476971630,"identity":"ee04290e-b4f2-47df-91fe-716f8b7ab1bd","order_by":5,"name":"Guadalupe Bribiesca-Contreras","email":"","orcid":"","institution":"National Oceanography Centre","correspondingAuthor":false,"prefix":"","firstName":"Guadalupe","middleName":"","lastName":"Bribiesca-Contreras","suffix":""},{"id":476971631,"identity":"07c19719-e028-419e-b17a-5ae1ffad38a7","order_by":6,"name":"Rishi Vachaspathy Astakala","email":"","orcid":"","institution":"University of Aberdeen","correspondingAuthor":false,"prefix":"","firstName":"Rishi","middleName":"Vachaspathy","lastName":"Astakala","suffix":""},{"id":476971632,"identity":"f7abf4ce-8486-4641-b442-c2c77e187736","order_by":7,"name":"Adrian Glover","email":"","orcid":"https://orcid.org/0000-0002-9489-074X","institution":"Natural History Museum, London","correspondingAuthor":false,"prefix":"","firstName":"Adrian","middleName":"","lastName":"Glover","suffix":""},{"id":476971633,"identity":"b1cfae49-5626-4320-9bde-66e3e7e1b71b","order_by":8,"name":"Marcel Jaspars","email":"","orcid":"https://orcid.org/0000-0002-2426-6028","institution":"University of Aberdeen","correspondingAuthor":false,"prefix":"","firstName":"Marcel","middleName":"","lastName":"Jaspars","suffix":""},{"id":476971634,"identity":"a9eb0bb8-96dd-4fbe-996e-0de42dc67b9e","order_by":9,"name":"Jonathan Copley","email":"","orcid":"https://orcid.org/0000-0003-3333-4325","institution":"University of Southampton","correspondingAuthor":false,"prefix":"","firstName":"Jonathan","middleName":"","lastName":"Copley","suffix":""}],"badges":[],"createdAt":"2025-06-26 14:20:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6984270/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6984270/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85932816,"identity":"187c697d-5bc5-40ca-9d24-9fff71884871","added_by":"auto","created_at":"2025-07-03 09:42:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3874656,"visible":true,"origin":"","legend":"\u003cp\u003eGlobal distribution of 2907 published records of Marine Natural Products (MNPs) from deep-sea organisms: (a) distribution of records by depth, compared with ocean area and accumulated global area [ref Weatherall et al., 2014]\u003csup\u003e8\u003c/sup\u003e; (b) territorial distribution, in relation to Exclusive Economic Zones (EEZs) of nations in the ocean, and geomorphological features according to the Esri hosted 2014 GRID-Arendal map [ref Harris, 2014]\u003csup\u003e92\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6984270/v1/c80e94074a99f8103b84794d.png"},{"id":85932815,"identity":"e55124d2-beee-4532-95e1-b4034cc23540","added_by":"auto","created_at":"2025-07-03 09:42:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":384597,"visible":true,"origin":"","legend":"\u003cp\u003eTaxonomic distributions of 2907 published records of Marine Natural Products (MNPs) from deep-sea organisms, showing abundances of deep-sea MNPs by phylum across 4 Kingdoms.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6984270/v1/8232b8974f4f8527bf2d4896.png"},{"id":85933048,"identity":"8adf6821-cb95-481e-ad12-5f953b310b6e","added_by":"auto","created_at":"2025-07-03 09:50:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":672845,"visible":true,"origin":"","legend":"\u003cp\u003eTaxonomic distributions of the characteristics of 2907 published records of Marine Natural Products (MNPs) from deep-sea organisms, generated using iTOL v6.9.1 [ref Letunic \u0026amp; Bork, 2024]\u003csup\u003e94\u003c/sup\u003e: (a) abundances of bioactive compounds, novel structures, and bioactive extracts by genus; (b) abundances of structures of deep-sea MNPs by genus; (c) abundances of bioactivities of deep-sea MNPs by genus.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6984270/v1/8fc953019db3896987776759.png"},{"id":85933049,"identity":"865c5544-763e-434e-8417-12a29fc8b909","added_by":"auto","created_at":"2025-07-03 09:50:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":5364345,"visible":true,"origin":"","legend":"\u003cp\u003eCluster plot of deep-sea organisms recorded as sources of novel and/or bioactive compounds, generated using DataWarrior v06.02.01 [ref Sander et al., 2015]\u003csup\u003e95\u003c/sup\u003e using a skelspheres descriptor with a 90% similarity index. Links and positioning in (a) show similarity of structural scaffolds; (b) displays associated phyla.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6984270/v1/b4422a71e1fd22d7f8883b0f.png"},{"id":85932819,"identity":"f3e5b8d9-8047-425e-8d97-1858b280c560","added_by":"auto","created_at":"2025-07-03 09:42:16","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1101889,"visible":true,"origin":"","legend":"\u003cp\u003ePhylogenetic relationship of 80 deep-sea organisms for which genetic data are available that are sources of Marine Natural Products (MNPs): (a) phylogeny of species in relation to geological time generated by TimeTree [ref Kumar, S. \u003cem\u003eet al.\u003c/em\u003e, 2022]\u003csup\u003e90\u003c/sup\u003e; (b) chemical pathways of MNPs for each species; (c) bioactivities of MNPs for each species.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6984270/v1/770e547f9794a3bcefdf618d.png"},{"id":85932823,"identity":"d5a2c3a3-a280-465e-9a72-1edadc091984","added_by":"auto","created_at":"2025-07-03 09:42:16","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1282698,"visible":true,"origin":"","legend":"\u003cp\u003eVariation in bioactivity profiles of deep-sea Marine Natural Products: (a) non-metric multidimensional scaling (nMDS) combined with K-means cluster analysis for bioactivity profiles, identifying five clusters (C1-5) in the dataset; (b) composition of clusters by phylogenetic source; (c) composition of clusters by environmental source; (d) composition of clusters by activity type.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6984270/v1/38d149fbd38762048f625e4c.png"},{"id":86141854,"identity":"92f36c3c-54b3-43ba-9e20-049f97797d9b","added_by":"auto","created_at":"2025-07-07 08:28:59","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3060920,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Globaldistributionofdeepseanaturalproductsshowsenvironmentalandphylogeneticundersamplingandpotentialforbiodiscovery.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6984270/v1_covered_1449ca08-2b3b-4365-9b9a-c929a7473a30.pdf"},{"id":85932814,"identity":"05e044a6-f610-464d-90fd-bec364a187e0","added_by":"auto","created_at":"2025-07-03 09:42:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":56860,"visible":true,"origin":"","legend":"Supplementary Material: Data Summary","description":"","filename":"SupplementaryMaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6984270/v1/bc8154a32c11ff0743f9268d.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Global distribution of deep-sea natural products shows environmental and phylogenetic undersampling and potential for biodiscovery","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6984270/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6984270/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Natural products from marine and terrestrial organisms provide an important resource for medicinal chemistry and drug discovery. Defined as occurring at depths greater than 200 m, most of the ocean, by area and volume, is comprised of deep-sea environments. These contrasting ecosystems exhibit a wide range of temperature, pressure, and environmental chemistry conditions that harbour high phylogenetic diversity. Here we analyse the global distribution of Marine Natural Products (MNPs) from deep-sea organisms, which reveals chronic undersampling of the deep ocean as a reservoir of structural novelty and diverse bioactivity. The sources of 2907 compounds and extracts, compiled from published records, show a sampling bias towards benthic and shallower deep-sea habitats, with relatively few from areas beyond national jurisdictions and a concentration of records along geomorphological features that have been the focus of marine scientific interest such as seamounts and hydrothermal vents. The phylogenetic distribution of deep-sea MNPs is dominated by non-metazoan sources (76% of records) and Ascomycota fungi in particular (55%). Polyketides are the most prevalent metabolites in deep-sea MNPs, and cytotoxic and antibacterial properties are the most commonly reported bioactivities. Our analyses highlight a need for systematic sampling and consistent data reporting to explore potential relationships between structural novelty, bioactivity, phylogeny and deep-sea environmental conditions, which could guide targeted biodiscovery in our planet's largest biome and enable better assessment of the benefits of protecting deep-sea biodiversity from human impacts.","manuscriptTitle":"Global distribution of deep-sea natural products shows environmental and phylogenetic undersampling and potential for biodiscovery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-03 09:42:12","doi":"10.21203/rs.3.rs-6984270/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1a03cfdf-7578-43a8-8b46-925f68ca6e41","owner":[],"postedDate":"July 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":50650114,"name":"Biological sciences/Chemical biology/Natural products"},{"id":50650115,"name":"Biological sciences/Drug discovery"}],"tags":[],"updatedAt":"2025-07-09T10:11:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-03 09:42:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6984270","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6984270","identity":"rs-6984270","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}