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Efficient synthesis of a (S)-fluoxetine intermediate using carbonyl reductase coupled with glucose dehydrogenase

Author:
Tang, Yunping, Zhang, Guomei, Wang, Zheng, Liu, Dan, Zhang, Linglu, Zhou, Yafeng, Huang, Ju, Yu, Fangmiao, Yang, Zuisu, Ding, Guofang
Source:
Bioresource technology 2018 v.250 pp. 457-463
ISSN:
0960-8524
Subject:
Escherichia coli, NAD (coenzyme), Sphingomonas, batch fermentation, buffers, enzyme activity, fermenters, glucose, pH
Abstract:
(S)-3-chloro-1-phenyl-1-propanol ((S)-CPPO) is an important chiral intermediate predominantly used in the synthesis of the chiral side chain of (S)-fluoxetine. In this study, carbonyl reductase (CBR) from Novosphingobium aromaticivorans was successfully expressed in recombinant E. coli. The enzymatic activity of the recombinant CBR was significantly increased to 1875 U/mL in the fed-batch fermentation in a 10 L fermenter and recombinant CBR was then purified and characterized. By regenerating NADH with glucose dehydrogenase, 100 g/L 3-chloro-1-phenyl-1-propanone (3-CPP) was successfully converted to (S)-CPPO with a conversion of 100% and ee value of 99.6% after 12 h at 30 °C in PBS buffer (pH 7.0), which are the highest reported to date for the bio-production of (S)-CPPO and presented great potential for green production of (S)-CPPO at industrial scale.
Agid:
5859168