A Single Point Mutation Reverses the Enantiopreference of Thermoanaerobacter ethanolicus Secondary Alcohol Dehydrogenase

摘要

Alcohol dehydrogenases (ADHs) are enzymes that catalyze the reversible reduction of carbonyl compounds to their corresponding alcohols. It is beyond doubt that they are important biocatalysts in asymmetric synthesis. Recent reports have shown that it is possible to use a number of ADHs for synthetic applications in nonaqueous media with high activities, which make them attractive choices to organic chemists. The stereopreferences of ADHs can be predicted by Prelog's rule (Figure 1), which depends on the relative sizes of the two substituents at a prochiral ketone or those at the stereocenter of a secondary alcohol. Very few ADHs show anti-Prelog ster-eopreference.For this reason, aside from the equal importance of both enantiomers, it is of great interest to search for or to engineer ADHs with anti-Prelog enantioselectivity. Owing to their applications as catalysts in asymmetric synthesis, it is also of great interest to expand the substrate specificity of ADHs.