Enzymatic synthesis of pharmacologically relevant chiral sulfoxides by improved Cb BVMO variants.

Baeyer-Villiger monooxygenases (BVMOs) are able to catalyse the asymmetric oxidation of sulfides. This property has made them attractive catalysts for the synthesis of chiral sulfoxide drugs. Here, we have designed and synthesised an exhaustive combinatorial mutant library of the previously identified lansoprazole sulfide monooxygenase Cb BVMO V1 . From this synthetic combinatorial mutant library, the best mutant, Cb BVMO V3 , was selected with a specific activity of approximately 1 U mg -1 for lansoprazole sulfoxides. We then optimised the reaction conditions of a two-phase system, achieving the enzymatic asymmetric synthesis of ( R )-lansoprazole in a space-time yield of 213 g L -1 d -1 and an enantiomeric excess of >99% ( R ) with no detectable by-products. In addition, Cb BVMO V3 showed higher activity towards other prazole sulfides. These results indicate the potential application of Cb BVMO in the chiral sulfoxide drug industry.