A Wagner-Meerwein-like rearrangement shapes the structures of the fischerazoles, cyanobacterial polychlorinated lipopeptides

A Wagner-Meerwein-like rearrangement shapes the structures of the fischerazoles, cyanobacterial polychlorinated lipopeptides | Research Square 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Article A Wagner-Meerwein-like rearrangement shapes the structures of the fischerazoles, cyanobacterial polychlorinated lipopeptides Pedro Leao, Sandra Figueiredo, Kathleen Abt, Konrad Viehrig, Peter Jervis, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8853700/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 The discovery of structurally unusual natural products inspires both the search for novel enzymatic transfor-mations and for new synthetic strategies. Here, we employ stable isotope-labeled precursor feeding and metabolomics to reveal highly unusual cyanobacterial lipopeptides – fischerazoles A-C. These metabolites con-tain a polychlorinated fatty acyl-derived moiety with a vinyl branch and an N-methylated carboxamide-thiazole terminus. Most strikingly, stable-isotope-labeled precursor supplementation showed that during fischerazole biosynthesis, a linear, hexadecanoic acid-derived intermediate is processed to yield the ultimately branched alkyl moiety. The branched-out carbon becomes part of the vinyl group together with an S-adenosyl methionine (SAM)-derived carbon. A polyketide synthase/non-ribosomal peptide synthetase (PKS/NRPS) biosynthetic gene cluster (BGC) associated with the fischerazoles was identified. In vitro assays revealed that the SAM depend-ent methyltranfesrae FshF catalyzes the alkyl chain rearrangement and concomitant vinyl group formation of an ACP-tethered unsaturated fatty acid. FshF-like enzymes, which are related to the well-characterized cyclo-propane fatty acid synthases (CFASs) can thus be explored for alkyl chain functionalization. Physical sciences/Chemistry/Chemical biology/Natural products Physical sciences/Chemistry/Biosynthesis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SIPreprintfischerazolesv5.pdf Supplementary Information 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 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

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