Biotransformation of a crizotinib intermediate using a mutant alcohol dehydrogenase of Lactobacillus kefir coupled with glucose dehydrogenase |
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| Authors: | Chuhong Zong Xu Zhang Fei Yang Yafeng Zhou Nan Chen Zuisu Yang |
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| Institution: | 1. Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, China;2. Microbiology Institute of Shaanxi Shaanxi Academy of Sciences, Xi'an, China;3. Hangzhou Obstetrics and Gynecology Hospital, Hangzhou, China |
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| Abstract: | Abstract(S)-1-(2, 6-dichloro-3-fluorophenyl) ethanol, the key chiral intermediate of crizotinib, was prepared from 1-(2, 6-dichloro-3-fluorophenyl) ethanone using the alcohol dehydrogenases from Lactobacillus kefir (ADH-LK) with a tetrad mutant (ADH-LKM, F147L/Y190P/V196L/A202W), coupled with glucose dehydrogenase (GDH). In the present study, ADH-LKM and GDH were successfully heterologous expressed in recombinant Escherichia coli. During the regeneration of NADPH with GDH, 150?g/L substrate was totally transformed into target chiral alcohol with an enantiomeric excess value of 99.9% after 12?h at 30?°C (pH 7.0). Our study demonstrates the potential for industrial green production of the key chiral intermediate of crizotinib. |
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| Keywords: | Alcohol dehydrogenase glucose dehydrogenase 1-(2 6-dichloro-3-fluorophenyl) ethanone (S)-1-(2 6-dichloro-3-fluorophenyl) ethanol Crizotinib |
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