CYCLOHEXANONE MONOOXYGENASE - A USEFUL REAGENT FOR ASYMMETRIC BAEYER-VILLIGER REACTIONS

Acinetobacter sp. NCIB 9871 cyclohexanone monooxygenase catalyzes the Baeyer-Villiger oxidations of a wide variety of ketones to the corresp onding lactones, many of which are valuable chiral building blocks. Th is enzyme accepts cyclobutanones, cyclopentanones, cyclohexanones and several bicyclic ketones as substrates. In most cases, the lactones ar e produced in high yields and optical purities. This review summarizes all of the published Baeyer-Villiger oxidations catalyzed by cyclohex anone monooxygenase published before mid-1997. An important recent fin ding is that the enzyme is very proficient at kinetically resolving ra cemic 2- and 3-substituted cyclohexanones. This provides one of the si mplest routes to optically pure substituted epsilon-caprolactones. Unf ortunately, the need to handle the pathogenic Acinetobacter strain as well as the lime and expense necessary to purify the enzyme and regene rate the reduced nicotinamide cofactor have hindered the acceptance of cyclohexanone monooxygenase as a synthetic reagent. To overcome these problems, the enzyme has been expressed in baker's yeast so that whol e yeast cells can be used for Baeyer-Villiger oxidations in place of t he purified enzyme or the Acinetobacter cells. The engineered yeast ap proach requires no biochemical expertise or equipment beyond that foun d in a normal laboratory. Finally, active site models of the enzyme ar e discussed. These allow one to predict the outcome of proposed reacti ons based on the results summarized here.