Aromatic polyketide biosynthesis: fidelity, evolution and engineering

Zhiwei Qin, Rebecca Devine, Matthew I. Hutchings and Barrie Wilkinson

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Mar 19, 2019
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Received Date: 11th March 19

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.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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