Unraveling the Fungal Strategy for Tetrahydroxanthone Biosynthesis and Diversification.

In vivo and in vitro reconstitution of the biosynthesis of fungal tetrahydroxanthones (THXs), blennolides A and C, led to the identification and characterization of the key enzymes for THX biosynthesis and diversification. The unusual isomerase NsrQ plays a crucial role in the THX skeleton synthesis probably by catalyzing the 1,2-hydride shift and methyl group epimerization, thus allowing dearomatizing cyclization to provide the THX architecture.