Genome Mining Discovery of a C-Alkylated Dihydroisocoumarin Pathway in Fungi.

A fungal C-alkylated dihydroisocoumarin pathway was discovered and elucidated. This pathway includes the following (1) a nonreducing polyketide synthase and a P450 collaboratively synthesize hydroxylated C-methylated isocoumarin ; (2) a methyltransferase methylates to ; and (3) importantly, an esterase specifically catalyzes a ring reconstruction process of to C-alkylated dihydroisocoumarin . Our discovery fills the gap in the enzymatic transformation process of natural C-alkylated isocoumarin derivates.