Biooxidation of Bridged Cycloketones Using Baeyer−Villiger Monooxygenases of Various Bacterial Origin

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.