Structural basis for the selective addition of an oxygen atom to cyclic ketones by Baeyer-Villiger monooxygenase from Parvibaculum lavamentivorans

Baeyer-Villiger monooxygenase (BVMO) catalyzes insertion of an oxygen atom into aliphatic or cyclic ketones with high regioselectivity. The BVMOs from Parvibaculum lavamentivorans (BVMO _Parvi ) and Oceanicola batsensis (BVMO _Ocean ) are interesting because of their homologies, with >40% sequence identity, and reaction with the same cyclic ketones with a methyl moiety to give different products. The revealed BVMO _Parvi structure shows that BVMO _Parvi forms a two-domain structure like other BVMOs. It has two inserted residues, compared with BVMO _Ocean , that form a bulge near the bound flavin adenine dinucleotide in the active site. Furthermore, this bulge is linked to a nearby α-helix via a disulfide bond, probably restricting access of the bulky methyl group of the substrate to this bulge. Another sequence motif at the entrance of the active site (Ala-Ser in BVMO _Parvi and Ser-Thr in BVMO _Ocean ) allows a large volume in BVMO _Parvi . These minute differences may discriminate a substrate orientation in both BVMOs from the initial substrate binding pocket to the final oxygenation site, resulting in the inserted oxygen atom being in different positions of the same substrate.