大肠杆菌中生物药物的生产现状及展望

doi:10.13560/j.cnki.biotech.bull.1985.2016.08.007

摘要/Abstract

摘要： 大肠杆菌是表达药用异源蛋白的首选微生物,此宿主目前已生产约30%被批准的药用蛋白。大肠杆菌具有生长迅速、产率高、效益大及易扩大培养的优势,促使它成为生物技术行业中蛋白大规模生产常选择的表达宿主。但大肠杆菌中密码子偏好性的存在及糖基化、磷酸化和蛋白水解加工等翻译后修饰的缺乏会限制其生产较复杂的重组生物药物。综述了大肠杆菌表达系统中几项满足生物技术产业需求的相关创新技术,介绍如何利用相关技术进步使大肠杆菌糖基化异源蛋白和表达包括全长糖基化抗体在内的复杂蛋白的过程,并对存在的问题及其研究前景进行展望,旨在为帮助大肠杆菌顺利生产更复杂的药用糖基化蛋白。

关键词: 大肠杆菌, 生物制药学, 密码子偏好性, 分子伴侣

Abstract: Escherichia coli is the most preferred microorganism to express heterologous protein for therapeutic use,as around 30% of the approved therapeutic proteins are currently being produced using it as a host. Due to its rapid growth,high yield,cost-effectiveness,and easy scale-up process,E. coli is chosen as an expression host in biotech industry for large-scale production of proteins. However,codon preference in E. coli and absences of post-translational modifications,such as glycosylation,phosphorylation and proteolytic processing limit its use for the production of slightly complex recombinant biopharmaceuticals. On purpose of helping E. coli to produce more complex and also glycosylated proteins for therapeutic use,this review summarizes the several novel technological advancements meeting the requirements of biotech industry,mainly focusing on the process of E. coli glycosylating heterologous proteins and expressing complex proteins including full-length glycosylated antibodies via those advancements. Further potential problems and prospects of futures researches are also discussed.

Key words: Escherichia coli, biopharmaceuticals, codon preference, molecular chaperones

蔡东梅,龚国利. 大肠杆菌中生物药物的生产现状及展望[J]. 生物技术通报, 2016, 32(8): 34-40.

CAI Dong-mei, GONG Guo-li. The Current Status and Future Perspectives of Production of Biopharmaceuticals in Escherichia coli[J]. Biotechnology Bulletin, 2016, 32(8): 34-40.

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