Biooxidation of bridged cycloketones using Baeyer-Villiger monooxygenases of various bacterial origin

Abstract

Bridged cycloketones were synthesized and utilized as substrates to study biooxidations mediated by Baeyer-Villiger monooxygenases (BVMO) of various bacterial origin. The required enzymes were heterologously produced by recombinant overexpression systems based on Escherichia coli to enable facile recycling of the required nicotinamide cofactors during the whole-cell biotransformations. Ketone precursors of various structural demands were chosen to evaluate steric limitations and flexibility of the active site of BVMOs. By desymmetrization of the prochiral substrates, four to six stereogenic centers were generated within a single biooxidation step. The enzyme library investigated in this study allowed access to antipodal lactone products with excellent enantioselectivity in several cases. Together with a distinct substrate acceptance profile, the recently proposed classification into two groups of cycloketone converting BVMOs was supported by the biotransformation results obtained within this study.