Formicamycin biosynthesis involves a unique reductive ring contraction

Qin, Zhiwei, Devine, Rebecca, Booth, Thomas, Farrar, Elliot, Grayson, Matthew, Hutchings, Matt and Wilkinson, Barrie (2020) Formicamycin biosynthesis involves a unique reductive ring contraction. Chemical Science, 11 (31). pp. 8125-8131. ISSN 2041-6520

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Fasamycin natural products are biosynthetic precursors of the formicamycins. Both groups of compounds are polyketide natural products that exhibit potent antibacterial activity despite displaying different three-dimensional topologies. We show here that transformation of fasamycin into formicamycin metabolites requires two gene products and occurs via a novel two-step ring expansion-ring contraction pathway. Deletion of forX, encoding a flavin dependent monooxygenase, abolished formicamycin production and leads to accumulation of fasamycin E. Deletion of the adjacent gene forY, encoding a flavin dependent oxidoreductase, also abolished formicamycin biosynthesis and led to the accumulation of new lactone metabolites that represent Baeyer-Villiger oxidation products of the fasamycins. These results identify ForX as a Baeyer-Villiger monooxygenase capable of dearomatizing ring C of the fasamycins. Through in vivo cross feeding and biomimetic semi-synthesis experiments we showed that these lactone products represent biosynthetic intermediates that are reduced to formicamycins in a unique reductive ring contraction reaction catalyzed by ForY.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Molecular Microbiology
Faculty of Science > Research Groups > Organisms and the Environment
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Depositing User: LivePure Connector
Date Deposited: 17 Jun 2020 00:13
Last Modified: 14 May 2023 00:26
DOI: 10.1039/D0SC01712D


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