Two enantiocomplementary Baeyer-Villiger monooxygenases newly identified for asymmetric oxyfunctionalization of thioether

Abstract

• Thermostable Am BVMO and Ra BVMO were identified by gene mining. • Am BVMO and Ra BVMO have opposite enantioselectivity toward thioanisole. • Ra BVMO displays high enantioselectivity toward ortho, meta, para -substituted thioanisoles. Two enantiocomplementary Baeyer-Villiger monooxygenases Ra BVMO and Am BVMO were identified by genome mining for the asymmetric sulfoxidation. Both recombinant BVMOs have optimal pH of 9.0 and temperature of 35 °C. The half-lives of Ra BVMO and Am BVMO at 30 °C were 24.4 and 24.6 h. Ra BVMO and Am BVMO exhibited broad substrate spectrum and could catalyze the oxidization of various compounds including fatty ketones, cyclic ketones, and thioethers. Kinetic parameters analysis revealed that both Ra BVMO and Am BVMO displayed higher catalytic efficiency toward thioanisole than cyclohexanone. As much as 50 mM thioanisole could be completely oxidized by Am BVMO and Ra BVMO with 99% ( R ) and 95% ( S ), respectively. Molecular docking analysis further provides evidence for the complementary enantioselectivity of Ra BVMO and Am BVMO. Our results demonstrate the potential application of the two novel BVMOs in asymmetric synthesis of sulfoxides.