New bioorganic reagents: evolved cyclohexanone monooxygenase--why is it more selective?

Four mutants of the cyclohexanone monooxygenase (CHMO) evolved as catalysts for Baeyer-Villiger oxidation of 4-hydroxycyclohexanone were investigated as catalysts for a variety of 4-substituted and 4,4-disubstituted cyclohexanones. Several excellent catalytic matches (mutant/substrate) were identified. The most important, however, is the finding that, in a number of cases, a mutant with a single exchange, Phe432Ser, was shown to be as robust and more selective as a catalyst than the wild-type CHMO. All biotransformations were performed on a laboratory scale, allowing full characterization of the products. The absolute configurations of two products were established. A model suggesting a possible role of the 432 serine residue in enantioselectivity control is proposed.