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.
Kayser
Margaret M
MM
Department of Physical Sciences, University of New Brunswick, Saint John, New Brunswick, E2L 4L5 Canada. kayser@unbsj.ca
Clouthier
Christopher M
CM
D019943:Amino Acid Substitution; D001665:Binding Sites; D002384:Catalysis; D003512:Cyclohexanones / Q000737:chemistry*; D019020:Directed Molecular Evolution / Q000379:methods*; D008956:Models, Chemical; D015394:Molecular Structure; D009154:Mutation; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000737:chemistry* / Q000235:genetics*; D013237:Stereoisomerism; D013379:Substrate Specificity
D003512:Cyclohexanones; D010105:Oxygenases; C019961:cyclohexanone oxygenase