Epoxide Stereochemistry Controls Regioselective Ketoreduction in Epoxyquinoid Biosynthesis.

ABSTRACT: Epoxyquinoids possess multiple contiguous chiral centers and reactive functional groups, offering valuable opportunities for drug discovery and chemical biology. Despite their structural diversity, the biosynthetic pathways of these species remain poorly understood. Here, we fully elucidate the biosynthesis of (-)-asperpentyn (2) through heterologous reconstitution in Aspergillus oryzae, chemical synthesis, chiral analysis, and biochemical assays. We identify critical pathway enzymes, including the FAD-binding monooxygenase AtyG, cupin domain-containing protein AtyE, and ketoreductases AtyD and AtyC. AtyE performs oxidation and stereoselective (2R,3S)-epoxidation, converting siccayne (4) to (2R,3S)-β-epoxyquinone (6). AtyD and AtyC co

SUBMITTER: Wang SY 

PROVIDER: S-EPMC12356543 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature