The fungal octaketide deoxyverrucosidin shares the same α-pyrone core with several nonaketides, including aurovertin, citreoviridin, and asteltoxin. Deoxyverrucosidin is featured by its unique epoxytetrahydrofuran ring. In this study, we demonstrate that this ring system is formed via a flavin-containing monooxygenase-mediated epoxidation on the polyene chain, followed by rearrangement with an epoxide expandase and a second epoxidation on the resulting 2,5-dihydrofuran ring with a cytochrome P450. This catalytic cascade differs clearly from the formation of dioxybicyclooctane or tetrahydrofuran motifs in other α-pyrone-containing metabolites, involving one flavin-containing monooxygenase and one hydrolase for up to two rounds epoxide ring formation and expansion.
