Metabolic engineering of Escherichia coli to improve recombinant protein production

被引:31
作者
Liu, Min [1 ,2 ]
Feng, Xinjun [1 ]
Ding, Yamei [3 ]
Zhao, Guang [1 ]
Liu, Huizhou [1 ]
Xian, Mo [1 ]
机构
[1] Chinese Acad Sci, Key Lab Biobased Mat, Qingdao Inst Bioenergy & Bioproc Technol, Qingdao 266101, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China
关键词
Recombinant protein production; Metabolic engineering; Workhorse selection; Stress factors; Carbon flux regulation; Growth retardation; CRA GENE KNOCKOUT; B STRAINS REL606; SMALL RNA; TRANSCRIPTIONAL REGULATION; PHOSPHOENOLPYRUVATE CARBOXYLASE; ACETATE ACCUMULATION; MOLECULAR CHAPERONES; GLUCOSE-TRANSPORTER; OVERFLOW METABOLISM; GLOBAL REGULATOR;
D O I
10.1007/s00253-015-6955-9
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Escherichia coli is one of the most widely used strains for recombinant protein production. However, obstacles also exist in both academic researches and industrial applications, such as the metabolic burden, the carbon source waste, and the cells' physiological deterioration. This article reviews recent approaches for improving recombinant protein production in metabolic engineering, including workhorse selection, stress factor application, and carbon flux regulation. Selecting a suitable host is the first key point for recombinant protein production. In general, it all depends on characteristics of the strains and the target proteins. It will be triggered cells physiological deterioration when the medium is significantly different from the cell's natural environment. Coexpression of stress factors can help proteins to fold into their native conformation. Carbon flux regulation is a direct approach for redirecting more carbon flux toward the desirable pathways and products. However, some undesirable consequences are usually found in metabolic engineering, such as glucose transport inhibition, cell growth retardation, and useless metabolite accumulation. More efficient regulators and platform cell factories should be explored to meet a variety of production demands.
引用
收藏
页码:10367 / 10377
页数:11
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