Asymmetric ketone reduction by a hyperthermophilic alcohol dehydrogenase. The substrate specificity, enantioselectivity and tolerance of organic solvents

In an effort to search for effective biocatalysts for asymmetric ketone reduction, the substrate specificity and enantioselectivity of an alcohol dehydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus have been evaluated. This hyperthermophilic alcohol dehydrogenase catalyzes the reduction of various ketones including aryl ketones, α- and β-ketoesters. Interestingly, aryl ketones, phenyl-substituted α- and β-ketoesters were reduced to the corresponding chiral alcohols in an enantiomerically pure form, while the substrates lacking phenyl groups were reduced with a moderate enantioselectivity. It thus suggests that a phenyl group next to the carbonyl group could be very helpful for achieving an excellent enantioselectivity, and this could provide valuable guidance for the future application of this useful enzyme through rational substrate engineering. The reaction temperature increased the enzyme activity, but exerted no effect on the enantioselectivity. This alcohol dehydrogenase also showed a high tolerance of organic solvents such as dimethyl sulfoxide, iso-propanol, methyl tert-butyl ether, and hexane, a particularly important and useful feature for the reduction of ketones with a low solubility in aqueous buffers.

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