Insights into Heterocycle Biosynthesis in the Cytotoxic Polyketide Alkaloid Janustatin A from a Plant-Associated Bacterium.

ABSTRACT: Janustatin A is a potently cytotoxic polyketide alkaloid produced at trace amounts by the marine bacterial plant symbiont Gynuella sunshinyii. Its biosynthetic terminus features an unusual pyridine-containing bicyclic system of unclear origin, in which polyketide and amino acid extension units appear reversed compared to the order of enzymatic modules in the polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) assembly line. To elucidate unknown steps in heterocycle formation, we first established robust genome engineering tools in G. sunshinyii. A combination of gene deletion, complementation, production improvement, and NMR experiments then demonstrated that two desaturase homologues, JanA and JanB, are involved in hydroxylation and pyridine formation by

SUBMITTER: Leopold-Messer S 

PROVIDER: S-EPMC11755721 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature