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Efficient Bioreduction of Ethyl 4-chloro-3-oxobutanoate to (S)4-chloro-3-hydrobutanoate by Whole Cells of Candida magnoliae in Water/ n-Butyl Acetate Two-phase System  

Xua Zhinan (Institute of Bioengineering, Department of Chemical and Biochemical Engineering, Zhejiang University)
Fang Limei (Zhejiang University City College)
Lin Jianping (Institute of Bioengineering, Department of Chemical and Biochemical Engineering, Zhejiang University)
Jiang Xiaoxia (Institute of Bioengineering, Department of Chemical and Biochemical Engineering, Zhejiang University)
Liu Ying (Institute of Bioengineering, Department of Chemical and Biochemical Engineering, Zhejiang University)
Cen Peilin (Institute of Bioengineering, Department of Chemical and Biochemical Engineering, Zhejiang University)
Publication Information
Biotechnology and Bioprocess Engineering:BBE / v.11, no.1, 2006 , pp. 48-53 More about this Journal
Abstract
The asymmetric biosynthesis of ethyl (S)-4-chloro-3-hydrobutanoate from ethyl 4-chloro-3-oxobutanoate was investigated by using whole cells of Candida magnoliae JX120-3 without the addition of glucose dehydrogenase or $NADP^+/NADPH$. In a one-phase system, the bioconversion yield was seriously affected on the addition of 12.1 g/L ethyl 4-chloro-3-oxobutanoate. In order to reduce this substrate inhibition, a water/ n-butyl acetate two-phase system was developed, and the bioreduction conditions optimized with regard to the yield and product enantiometric excess value. The optimal conditions were as following: water to n-butyl acetate volume ratio of 1:1, 4.0 g DCW/L active cells, 50 g/L glucose and $35^{\circ}C$. By adopting a dropwise substrate feeding strategy, high concentration of ethyl 4-chloro-3-oxobutanoate (60 g/L) could be asymmetrically reduced to ethyl (S)-4-chloro-3-hydrobutanoate with high yield (93.8%) and high enantiometric excess value (92.7%).
Keywords
asymmetric reduction; ethyl (S)-4-chloro-3-hydrobutanoate; ethyl 4-chloro-3-oxobut anoate; Candida magnoliae; two-phase system;
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