Discovery of a Dual Function Cytochrome P450 that Catalyzes Enyne Formation in Cyclohexanoid Terpenoid Biosynthesis

摘要

The 1,3-enyne moiety is commonly found in cyclohexanoid natural products produced by endophytic and plant pathogenic fungi. Asperpentyn (1) is a 1,3-enyne-containing cyclohexanoid terpenoid isolated fromAspergillusandPestalotiopsis. The genetic basis and biochemical mechanism of 1,3-enyne biosynthesis in1, and other natural products containing this motif, has remained enigmatic despite their potential ecological roles. Identified here is the biosynthetic gene cluster and characterization of two crucial enzymes in the biosynthesis of1. A P450 monooxygenase that has a dual function, to first catalyze dehydrogenation of the prenyl chain to generate acis-diene intermediate and then serve as an acetylenase to yield an alkyne moiety, and thus the 1,3-enyne, was discovered. A UbiA prenyltransferase was also characterized and it is unusual in that it favors transferring a five-carbon prenyl chain, rather than a polyprenyl chain, to ap-hydroxybenzoic acid acceptor.