Molecular Basis for Short-Chain Thioester Hydrolysis by Acyl Hydrolases in trans-Acyltransferase Polyketide Synthases.

ABSTRACT: Polyketide synthases (PKSs) are multidomain enzymatic assembly lines that biosynthesize a wide selection of bioactive natural products from simple building blocks. In contrast to their cis-acyltransferase (AT) counterparts, trans-AT PKSs rely on stand-alone ATs to load extender units onto acyl carrier protein (ACP) domains embedded in the core PKS machinery. Trans-AT PKS gene clusters also encode stand-alone acyl hydrolases (AHs), which are predicted to share the overall fold of ATs but function like type II thioesterases (TE_IIs), hydrolyzing aberrant acyl chains from ACP domains to promote biosynthetic efficiency. How AHs specifically target short acyl chains, in particular acetyl groups, tethered as thioesters to the substrate-shuttling ACP domains, with h

SUBMITTER: Fage CD 

PROVIDER: S-EPMC11775670 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature