A role for antibiotic biosynthesis monooxygenase domain proteins in fidelity control during aromatic polyketide biosynthesis

Zhiwei Qin, Rebecca Devine, Matthew Hutchings, Barrie Wilkinson

Research output: Contribution to journalArticle

6 Citations (Scopus)
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Abstract

We report the formicapyridines which are structurally and biosynthetically related to the pentacyclic fasamycin and formicamycin aromatic polyketides but comprise a rare pyridine moiety. These new compounds are trace level metabolites formed by derailment of the major biosynthetic pathway. Inspired by evolutionary logic we show that rational mutation of a single gene in the biosynthetic gene cluster leads to a significant increase both in total formicapyridine production and their enrichment relative to the fasamycins/formicamycins. Our observations broaden the polyketide biosynthetic landscape and identify a non-catalytic role for ABM superfamily proteins in type II polyketide synthase assemblages for maintaining biosynthetic pathway fidelity.
Original languageEnglish
Article number3611
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 9 Aug 2019

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