重组蛋白质在大肠杆菌体系中的可溶性表达策略<sup>*</sup>

doi:10.13523/j.cb.2305048

中国生物工程杂志

2023, Vol. 43

Issue (9): 33-45 DOI: 10.13523/j.cb.2305048

综述

重组蛋白质在大肠杆菌体系中的可溶性表达策略^*

苗朝悦,杜乐,王佳琦,陈梓杰,黄靖倍,陈且昕,邹沛璇,韩笑,张纯^**(

)

四川大学华西药学院靶向药物及释药系统教育部重点实验室成都 610041

Soluble Expression Strategies for Production of Recombinant Proteins in Escherichia coli

MIAO Zhao-yue,DU Le,WANG Jia-qi,CHEN Zi-jie,HUANG Jing-bei,CHEN Qie-xin,ZOU Pei-xuan,HAN Xiao,ZHANG Chun^**(

)

Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China

全文: PDF(841 KB) HTML

摘要：

大肠杆菌表达体系因其表达量高、周期短、成本低等诸多优势特征而被广泛用作重组异源蛋白质的表达宿主。据统计超过30%的重组蛋白质药物和50%重组蛋白质的制备是使用大肠杆菌作为表达宿主。蛋白质错误折叠或未折叠以及包涵体形成是大肠杆菌表达体系更广泛应用的主要阻碍。因此,重组蛋白质在大肠杆菌体系中可溶性表达策略探索意义重大。综述了重组蛋白质在大肠杆菌表达系统中不可溶性表达的原因、机制以及影响大肠杆菌表达系统重组蛋白质可溶性的一些关键因素,并基于外源蛋白质在大肠杆菌中表达的各个步骤,总结了目前促进蛋白质在大肠杆菌表达系统中高效、可溶性表达的策略,为进一步拓展大肠杆菌表达体系在重组异源蛋白质可溶性表达中的应用提供参考。

关键词： 大肠杆菌表达体系; 重组异源蛋白质; 可溶性表达; 包涵体; 糖基化

Abstract:

Escherichia coli expression system is widely used as the expression host of recombinant heterologous proteins because of its high expression level, short cycle, low cost and many other advantages. According to statistics, more than 30% of the recombinant protein drugs and 50% of the recombinant proteins were obtained by using E. coli as the expression host. The misfolding or unfolding of proteins and the formation of inclusion bodies are the main obstacles to the wider application of E. coli expression systems. Therefore, it is of great significance to explore the strategy of soluble expression of recombinant proteins in E. coli system. In this paper, the reasons and mechanisms of insoluble expression of recombinant proteins in E. coli expression system and some key factors affecting the solubility of recombinant proteins in E. coli expression system were reviewed. Based on the various steps of expression of foreign proteins in E. coli, the current strategies to promote efficient and soluble expression of proteins in E. coli expression system were summarized, with the aim to provide a reference for further expanding the application of E. coli expression system in the soluble expression of recombinant heterologous proteins.

Key words: Escherichia coli expression system Recombinant heterologous protein Soluble expression Inclusion bodies Glycosylation

收稿日期: 2023-05-31 出版日期: 2023-10-08

ZTFLH:

Q814

基金资助: * 国家自然科学基金(82003685);四川省科学技术厅项目(2021YJ0187)

通讯作者: ** 电子信箱:chunzhang@scu.edu.cn

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	苗朝悦
	杜乐
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	陈梓杰
	黄靖倍
	陈且昕
	邹沛璇
	韩笑
	张纯

引用本文:

苗朝悦, 杜乐, 王佳琦, 陈梓杰, 黄靖倍, 陈且昕, 邹沛璇, 韩笑, 张纯. 重组蛋白质在大肠杆菌体系中的可溶性表达策略^*[J]. 中国生物工程杂志, 2023, 43(9): 33-45.

MIAO Zhao-yue, DU Le, WANG Jia-qi, CHEN Zi-jie, HUANG Jing-bei, CHEN Qie-xin, ZOU Pei-xuan, HAN Xiao, ZHANG Chun. Soluble Expression Strategies for Production of Recombinant Proteins in Escherichia coli. China Biotechnology, 2023, 43(9): 33-45.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2305048 或 https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I9/33

图1 蛋白质折叠过程示意图

图2 影响重组蛋白质包涵体形成的因素

表1 大肠杆菌表达体系常用宿主亚型类型

表2 重组蛋白质表达常用融合标签类型

表3 大肠杆菌表达体系常用分子伴侣

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