Oxepinamide F biosynthesis involves enzymatic D-aminoacyl epimerization, 3H-oxepin formation, and hydroxylation induced double bond migration.

ABSTRACT: Oxepinamides are derivatives of anthranilyl-containing tripeptides and share an oxepin ring and a fused pyrimidinone moiety. To the best of our knowledge, no studies have been reported on the elucidation of an oxepinamide biosynthetic pathway and conversion of a quinazolinone to a pyrimidinone-fused 1H-oxepin framework by a cytochrome P450 enzyme in fungal natural product biosynthesis. Here we report the isolation of oxepinamide F from Aspergillus ustus and identification of its biosynthetic pathway by gene deletion, heterologous expression, feeding experiments, and enzyme assays. The nonribosomal peptide synthase (NRPS) OpaA assembles the quinazolinone core with D-Phe incorporation. The cytochrome P450 enzyme OpaB catalyzes alone the oxepin ring formation. The flavoenzyme OpaC installs su

SUBMITTER: Zheng L 

PROVIDER: S-EPMC7530659 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature