Assessing the substrate selectivities and enantioselectivities of eight novel Baeyer-Villiger monooxygenases toward alkyl-substituted cyclohexanones.
Genes encoding eight Baeyer-Villiger monooxygenases have recently been cloned from bacteria inhabiting a wastewater treatment plant. We have carried out a systematic investigation in which each newly cloned enzyme, as well as the cyclohexanone monooxygenase from Acinetobacter sp. NCIB 9871, was used to oxidize 15 different alkyl-substituted cyclohexanones. The panel of substrates included equal numbers of 2-, 3-, and 4-alkyl-substituted compounds to probe each enzyme's stereoselectivity toward a homologous series of synthetically important compounds. For all 4-alkyl-substituted cyclohexanones tested, enzymes were discovered that afforded each of the corresponding (S)-lactones in >/=98% ee. This was also true for the 2-alkyl-substituted cyclohexanones examined. The situation was more complex for 3-akyl-substituted cyclohexanones. In a few cases, single Baeyer-Villiger monooxygenases possessed both high regio- and enantioselectivities toward these compounds. More commonly, however, they showed only one type of selectivity. Nonetheless, enzymes with such properties might be useful as parts of a two-step bioprocess where an initial kinetic resolution is followed by a regioselective oxidation on the isolated, optically pure ketone.
Kyte
Brian G
BG
127 Chemistry Research Building, University of Florida, Gainesville, Florida 32611, USA.
Rouvière
Pierre
P
Cheng
Qiong
Q
Stewart
Jon D
JD
D003512:Cyclohexanones / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
D003512:Cyclohexanones; D006899:Mixed Function Oxygenases