Members of the abyssomicin class of natural products are characterized by a novel vinylic bridged ether ring. In this study, in vivo gene inactivation, structure elucidation of the accumulated intermediate abyssomicin 6, and in vitro enzyme assays enabled the identification of a cytochrome P450 enzyme, AbmV. AbmV carries out domino reactions involving bridged ether installation and C-11 hydroxylation during the biosynthesis of neoabyssomicins/abyssomicins in S. koyangensis SCSIO 5802.