Enhanced production of polysialic acid by metabolic engineering of Escherichia coli

Verfasser / Beitragende:
[Fang Chen, Yong Tao, Cheng Jin, Yang Xu, Bai-Xue Lin]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/6(2015-03-01), 2603-2611
Format:
Artikel (online)
ID: 605499063
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024 7 0 |a 10.1007/s00253-015-6391-x  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6391-x 
245 0 0 |a Enhanced production of polysialic acid by metabolic engineering of Escherichia coli  |h [Elektronische Daten]  |c [Fang Chen, Yong Tao, Cheng Jin, Yang Xu, Bai-Xue Lin] 
520 3 |a A number of reports have described the production of polysialic acid (PSA), focusing on the fermentation and purification of PSA. However, little work has been done to strengthen the synthetic pathway of PSA to improve PSA production. In this study, an efficient process for enhanced production of PSA using a recombinant Escherichia coli strain was developed. To improve the PSA production efficiency, the key enzymes of PSA synthetic pathway were overexpressed separately or in combination, including N-acetylneuraminate (Neu5Ac) 7-O(or 9-O)-acetyltransferase (NeuD), CMP-Neu5Ac synthetase (NeuA), and alpha-Neu5Ac alpha-2,8-sialyltransferase (NeuS). The PSA production was significantly improved by coexpression of NeuD and NeuA. In terms of the efficiency, NeuD was considered as the most important factor. Secondly, the competing pathway of intermediate Neu5Ac was blocked by nanA deletion. The efficient PSA-producing strain E. coli SA9ΔnanA/pDB1S-DA was constructed, and 16.15 ± 1.45g/L PSA was obtained in the fed-batch culture. The production of PSA by engineered strain was increased by 85% compared to the original strain. These results provide evidence for improvement of PSA production by regulation of the PSA biosynthetic pathway. The high productivity of our process should make it a promising cost-effective resource for PSA. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Polysialic acid  |2 nationallicence 
690 7 |a Escherichia coli  |2 nationallicence 
690 7 |a Metabolic engineering  |2 nationallicence 
690 7 |a Fed-batch fermentation  |2 nationallicence 
700 1 |a Chen  |D Fang  |u CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Chaoyang District, 100101, Beijing, People's Republic of China  |4 aut 
700 1 |a Tao  |D Yong  |u CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Chaoyang District, 100101, Beijing, People's Republic of China  |4 aut 
700 1 |a Jin  |D Cheng  |u The State Key Laboratory of Mycology (SKLM), Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, People's Republic of China  |4 aut 
700 1 |a Xu  |D Yang  |u Sino-Germany Joint Research Institute, Nanchang University, 330047, Nanchang, Jiangxi, China  |4 aut 
700 1 |a Lin  |D Bai-Xue  |u CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Chaoyang District, 100101, Beijing, People's Republic of China  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/6(2015-03-01), 2603-2611  |x 0175-7598  |q 99:6<2603  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6391-x  |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/s00253-015-6391-x  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Chen  |D Fang  |u CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Chaoyang District, 100101, Beijing, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tao  |D Yong  |u CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Chaoyang District, 100101, Beijing, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Jin  |D Cheng  |u The State Key Laboratory of Mycology (SKLM), Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Xu  |D Yang  |u Sino-Germany Joint Research Institute, Nanchang University, 330047, Nanchang, Jiangxi, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Lin  |D Bai-Xue  |u CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Chaoyang District, 100101, Beijing, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/6(2015-03-01), 2603-2611  |x 0175-7598  |q 99:6<2603  |1 2015  |2 99  |o 253