摘要：

Optically pure 1-phenyl-1,2-ethanediol is a very important chiral building block and intermediate in fine chemical and pharmaceutical industries. Reduction of 2-hydroxyacetophenone provides a straightforward approach to access these important compounds. In this study, two enantiocomplementary carbonyl reductases, BDHA (2,3-butanediol dehydrogenase from Bacillus subtilis ) and GoSCR (polyol dehydrogenase from Gluconobacter oxydans ) were discovered for the first time to convert 2-hydroxyacetophenone (2-HAP) to ( R )-1-phenyl-1,2-ethanediol (( R )-PED) and ( S )-1-phenyl-1,2-ethanediol (( S )-PED) with excellent stereochemical selectivity, respectively. The two enzymes were purified and characterized. In vitro bioreduction of 2-HAP catalyzed by BDHA and GoSCR coupled with glucose dehydrogenase (GDH) from Bacillus subtilis for cofactor regeneration were demonstrated, affording both ( R )-PED and ( S )-PED in>99% ee and 99% conversion. Recombinant Escherichia coli whole cells co-expressing both GDH and BDHA or GoSCR genes were used to asymmetric reduction of 2-HAP to ( R )-PED or ( S )-PED. Under the optimized conditions, the bioreduction of 400mM (54g/L) substrate was proceeded smoothly without the external addition of cofactor, and the product ( R )-PED and ( S )-PED were obtained with 99% yield, >99% ee and 18.0g/L/h volumetric productivity. These results offer a practical biocatalytic method for the preparation of both ( R )-PED and ( S )-PED with high volumetric productivity.

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