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. ISSN 2041-6520

[img]
Preview
PDF (Qin et al 2020_Chemical Science_Edge Article_revised_clean) - Submitted Version
Download (1MB) | Preview
[img]
Preview
PDF (Published_Version) - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

Abstract

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
Depositing User: LivePure Connector
Date Deposited: 17 Jun 2020 00:13
Last Modified: 06 Jul 2020 23:59
URI: https://ueaeprints.uea.ac.uk/id/eprint/75614
DOI: 10.1039/D0SC01712D

Actions (login required)

View Item View Item