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)
  • Published : 2006.01.01

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

References

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