A Bifunctional Cytochrome P450 Enzyme Catalyzes Hydroxylation and Aryl-Aryl Ether Formation in the Biosynthesis of Emestrin.

ABSTRACT: Emestrins, a subgroup of epipolythiodioxopiperazines, are originated from cyclo-l-Phe-l-Phe and feature a dihydrooxepine ring. They contain typically a 15-membered lactone ring with an aryl-aryl ether linkage. Despite considerable progress in elucidating epipolythiodioxopiperazine biosynthesis, the enzymatic mechanism for the ether bond formation in emestrins remains uncharacterized. We identified a putative gene cluster (eme) in the fungus Emericella quadrilineata with three unknown P450 enzymes, EmeE, EmeR, and EmeO. Gene deletion, feeding experiments, and in vitro assays proved that EmeE and EmeR install regioselective and stereospecific hydroxyl groups at the ß-positions of the diketopiperazine ring. EmeO acts as a bifunctional enzyme for the construction of the lactone ring via an ary

SUBMITTER: Chen YC 

PROVIDER: S-EPMC12910431 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature