Highly efficient synthesis of chiral alcohols with a novel NADH-dependent reductase from Streptomyces coelicolor |
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Authors: | Wang Li-Juan Li Chun-Xiu Ni Yan Zhang Jie Liu Xiang Xu Jian-He |
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Institution: | a Laboratory of Biocatalysis and Synthetic Biotechnology, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China b School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China |
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Abstract: | An NADH-dependent reductase (ScCR) from Streptomyces coelicolor was discovered by genome mining for carbonyl reductases. ScCR was overexpressed in Escherichia coli BL21, purified to homogeneity and its catalytic properties were studied. This enzyme catalyzed the asymmetric reduction of a broad range of prochiral ketones including aryl ketones, α- and β-ketoesters, with high activity and excellent enantioselectivity (>99% ee) towards β-ketoesters. Among them, ethyl 4-chloro-3-oxobutanoate (COBE) was efficiently converted to ethyl (S)-4-chloro-3-hydroxybutanoate ((S)-CHBE), an important pharmaceutical intermediate, in water/toluene biphasic system. As much as 600 g/L (3.6 M) of COBE was asymmetrically reduced within 22 h using 2-propanol as a co-substrate for NADH regeneration, resulting in a yield of 93%, an enantioselectivity of >99% ee, and a total turnover number (TTN) of 12,100. These results indicate the potential of ScCR for the industrial production of valuable chiral alcohols. |
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Keywords: | Carbonyl reductase Streptomyces coelicolor Asymmetric reduction Ethyl (S)-4-chloro-3-hydroxybutanoate NADH regeneration |
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