A Hooker Oxygenase Archetype in Polyketide Biosynthesis Challenging the Baeyer-Villiger Monooxygenase Paradigm.

ABSTRACT: Aromatic polyketides from Actinobacteria are structurally complex bioactive natural products with significant therapeutic potential, whose biosynthesis involves polyketide chain assembly, keto reduction, cyclization, and aromatization. This is followed by pathway-specific enzymatic tailoring steps, occasionally including rare oxidative rearrangements of the carbon skeleton, as exemplified by the rishirilides. In this study, we investigate RslO9, a flavin-dependent tailoring key enzyme of rishirilide biosynthesis, previously hypothesized to facilitate a lactone-forming Baeyer-Villiger oxidation of the rishirilide naphthoquinone core and subsequent intramolecular aldol condensation. Through detailed investigation of RslO9's mechanism, structural features, and substrate scope, we unexpectedly

SUBMITTER: Weddeling HG 

PROVIDER: S-EPMC12903851 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature