Erschienen in:Angewandte Chemie International Edition
Sprache:
Englisch
DOI:
10.1002/anie.202116614
ISSN:
1433-7851;
1521-3773
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Bacterial multimodular polyketide synthases (PKSs) are large enzymatic assembly lines that synthesize many bioactive natural products of therapeutic relevance. While PKS catalysis is mostly based on fatty acid biosynthetic principles, polyketides can be further diversified by post‐PKS enzymes. Here, we characterized a remarkably versatile <jats:italic>trans</jats:italic>‐acyltransferase (<jats:italic>trans</jats:italic>‐AT) PKS from <jats:italic>Serratia</jats:italic> that builds structurally complex macrolides via more than ten functionally distinct PKS modules. In the oocydin PKS, we identified a new oxygenation module that α‐hydroxylates polyketide intermediates, a halogenating module catalyzing backbone γ‐chlorination, and modular <jats:italic>O</jats:italic>‐acetylation by a thioesterase‐like domain. These results from a single biosynthetic assembly line highlight the expansive biochemical repertoire of <jats:italic>trans</jats:italic>‐AT PKSs and provide diverse modular tools for engineered biosynthesis from a close relative of <jats:italic>E. coli</jats:italic>.</jats:p>