Biosynthesis-Guided Discovery and Engineering of α-Pyrone Natural Products from Type I Polyketide Synthases.

ABSTRACT: Natural products containing the α-pyrone moiety are produced by polyketide synthases (PKSs) in bacteria, fungi, and plants. The conserved biosynthetic logic for the production of the α-pyrone moiety involves the cyclization of a triketide intermediate which also off-loads the polyketide from the activating thioester. In this study, we show that truncating a tetraketide natural product producing PKS assembly line allows for a thioesterase-independent off-loading of an α-pyrone polyketide natural product, one which we find to be natively present in the extracts of the bacterium that otherwise furnishes the tetraketide natural product. By engineering the truncated PKS in vitro, we demonstrate that a ketosynthase (KS) domain with relaxed substrate selectivity when coupled with in trans

SUBMITTER: Yi D 

PROVIDER: S-EPMC10204065 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature