A Berberine Bridge Enzyme-like Oxidase Mediates the Cage-like Acresorbicillinol C Biosynthesis

Oxosorbicillinol and cage-like acresorbicillinol C are bioactive sorbicillinoids produced by Acremonium chrysogenum. We found that a berberine bridge enzyme-like oxidase AcsorD was responsible for their biosynthesis by gene deletion and heterologous expression. AcsorD catalyzed oxidation of sorbicillinol to form oxosorbicillinol in in vitro assays, which was successively condensed with sorbicillinol to form acresorbicillinol C spontaneously. Finally, site-directed mutation revealed that Tyr525 was the key residue in the catalysis of the oxidation reaction and unlocking cage-like acresorbicillinol C production.