Evolution, structure and function of the biosynthetic gene cluster of myriocin, a potent inhibitory sphingolipid

Evolution, structure and function of the biosynthetic gene cluster of myriocin, a potent inhibitory sphingolipid | 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 Evolution, structure and function of the biosynthetic gene cluster of myriocin, a potent inhibitory sphingolipid Alexandra Brand, Ben Rutter, Michael Herrera, Gustavo Perez-Ortiz, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6881806/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Myriocin is a fungal secondary metabolite exploited worldwide as a powerful inhibitor of sphingolipid biosynthesis through its structural similarity to sphingosine. We identify the myriocin biosynthesis gene cluster (BGC) through de novo sequencing of two producing fungi, Isaria sinclairii and Mycelia sterilia, yielding genomes of 25.2 Mb and 34.2 Mb encoding 27 and 20 secondary metabolite BGCs, respectively. BGCs #5 in I. sinclairii and #18 in M. sterilia shared the Polyketide Synthase (PKS) and alpha oxo-amine synthase (AOS) predicted for myriocin biosynthesis, with 74 % and 79 % sequence similarity, respectively. Analysis of a 2,236 fungal genome database suggests the pathway originated in the Sordariomycete ancestor, presenting in two major clades distinguished by PKS gene orientation. The placement of thermophilic M. sterilia suggests myriocin BGC acquisition through horizontal gene transfer, but its origin in I. sinclairii is ambiguous. Heterologously-expressed IsMyrA bound amino-malonate and a protein-protein docking interface were identified between the acyl carrier protein and IsMyrA. A model of PKS domain function, the roles of the PKS and AOS genes and the synteny of the myriocin biosynthetic gene cluster across 34 carrier species of Ascomycetes is presented. Biological sciences/Chemical biology/Natural products/Natural product synthesis Biological sciences/Evolution/Population genetics/Genetic variation/Structural variation Biological sciences/Microbiology/Fungi/Fungal genomics Myriocin biosynthesis Isaria sinclairii Mycelia sterilia Polyketide synthase sphingolipid inhibitor Full Text Additional Declarations There is NO Competing Interest. Supplementary Files RutteretalMyriocinBiosynthesisSupplementaryMethods.pdf Rutter et al_Myriocin biosynthesis - Supplementary Methods SupplementaldataKonkelSlotB.xlsx Rutter et al_Myriocin biosynthesis_Dataset 1 Cite Share Download PDF Status: Under Review 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-6881806","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":478511487,"identity":"47ad6168-a394-41ec-a2d5-a97c71f9fef0","order_by":0,"name":"Alexandra 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