Upscale production of ethyl ( S )-4-chloro-3-hydroxybutanoate by using carbonyl reductase coupled with glucose dehydrogenase in aqueous-organic solvent system

Verfasser / Beitragende:
[Zhi-Qiang Liu, Jing-Jing Ye, Zhen-Yang Shen, Hua-Bin Hong, Jian-Bo Yan, Yi Lin, Zheng-Xu Chen, Yu-Guo Zheng, Yin-Chu Shen]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/5(2015-03-01), 2119-2129
Format:
Artikel (online)
ID: 605504296
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024 7 0 |a 10.1007/s00253-014-6245-y  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-014-6245-y 
245 0 0 |a Upscale production of ethyl ( S )-4-chloro-3-hydroxybutanoate by using carbonyl reductase coupled with glucose dehydrogenase in aqueous-organic solvent system  |h [Elektronische Daten]  |c [Zhi-Qiang Liu, Jing-Jing Ye, Zhen-Yang Shen, Hua-Bin Hong, Jian-Bo Yan, Yi Lin, Zheng-Xu Chen, Yu-Guo Zheng, Yin-Chu Shen] 
520 3 |a (S)-4-chloro-3-hydroxybutanoate ((S)-CHBE) is an important chiral intermediate to synthesize the side chain of cholesterol-lowering drug atorvastatin. To biosynthesize the (S)-CHBE, a recombinant Escherichia coli harboring the carbonyl reductase and glucose dehydrogenase was successfully constructed. The recombinant E. coli was cultured in a 500-L fermentor; after induction and expression, the enzyme activity and cell biomass were increased to 23,661.65U/L and 13.90g DCW/L which was 3.24 and 2.60-folds compared with those in the 50L fermentor. The biocatalytic process for the synthesis of (S)-CHBE in an aqueous-organic solvent system was constructed and optimized with a substrate fed-batch strategy. The ethyl 4-chloro-3-oxobutanoate concentration reached to 1.7M, and the (S)-CHBE with yield of 97.2% and enantiomeric excess (e.e.) of 99% was obtained after 4-h reaction in a 50-L reactor. In this study, the space-time yield and space-time yield per gram of biomass (dry cell weight, DCW) were 413.17mM/h and 27.55mM/h/g DCWfor(S)-CHBE production, respectively, which were the highest values as compared to previous reports. Finally, (S)-CHBE was extracted from the reaction mixture with 82% of yield and 95% of purity. This study paved the foundation for the upscale production of (S)-CHBE by biocatalysis method. 
540 |a Springer-Verlag Berlin Heidelberg, 2014 
690 7 |a Co-expression  |2 nationallicence 
690 7 |a Carbonyl reductase  |2 nationallicence 
690 7 |a Glucose dehydrogenase  |2 nationallicence 
690 7 |a Ethyl ( S )-4-chloro-3-hydroxybutanoate  |2 nationallicence 
700 1 |a Liu  |D Zhi-Qiang  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
700 1 |a Ye  |D Jing-Jing  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
700 1 |a Shen  |D Zhen-Yang  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
700 1 |a Hong  |D Hua-Bin  |u Zhejiang Neo-DanKong Pharmaceutical Co., Ltd, 318000, Taizhou, Zhejiang, People's Republic of China  |4 aut 
700 1 |a Yan  |D Jian-Bo  |u Zhejiang Neo-DanKong Pharmaceutical Co., Ltd, 318000, Taizhou, Zhejiang, People's Republic of China  |4 aut 
700 1 |a Lin  |D Yi  |u Zhejiang Neo-DanKong Pharmaceutical Co., Ltd, 318000, Taizhou, Zhejiang, People's Republic of China  |4 aut 
700 1 |a Chen  |D Zheng-Xu  |u Zhejiang Neo-DanKong Pharmaceutical Co., Ltd, 318000, Taizhou, Zhejiang, People's Republic of China  |4 aut 
700 1 |a Zheng  |D Yu-Guo  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
700 1 |a Shen  |D Yin-Chu  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/5(2015-03-01), 2119-2129  |x 0175-7598  |q 99:5<2119  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-014-6245-y  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-014-6245-y  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Liu  |D Zhi-Qiang  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ye  |D Jing-Jing  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Shen  |D Zhen-Yang  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Hong  |D Hua-Bin  |u Zhejiang Neo-DanKong Pharmaceutical Co., Ltd, 318000, Taizhou, Zhejiang, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yan  |D Jian-Bo  |u Zhejiang Neo-DanKong Pharmaceutical Co., Ltd, 318000, Taizhou, Zhejiang, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Lin  |D Yi  |u Zhejiang Neo-DanKong Pharmaceutical Co., Ltd, 318000, Taizhou, Zhejiang, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Chen  |D Zheng-Xu  |u Zhejiang Neo-DanKong Pharmaceutical Co., Ltd, 318000, Taizhou, Zhejiang, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zheng  |D Yu-Guo  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Shen  |D Yin-Chu  |u Institute of Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, Zhejiang, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/5(2015-03-01), 2119-2129  |x 0175-7598  |q 99:5<2119  |1 2015  |2 99  |o 253