Manufacturing of recombinant therapeutic proteins in microbial systems

被引：119

作者：

Novartis Biopharmaceutical Operations, Sandoz GmbH, Kundl, Austria ^{[1
]}

机构：

[1] Novartis Biopharmaceutical Operations, Sandoz GmbH, Kundl

来源：

Biotechnol. J. | 2006年 / 2卷 / 164-186期

关键词：

Downstream processing; Fermentation; In-process control; Microbial expression systems; Product characterization;

D O I：

10.1002/biot.200500051

中图分类号：

学科分类号：

摘要：

Recombinant therapeutic proteins have gained enormous importance for clinical applications. The first recombinant products have been produced in E. coli more than 20 years ago. Although with the advent of antibody-based therapeutics mammalian expression systems have experienced a major boost, microbial expression systems continue to be widely used in industry. Their intrinsic advantages, such as rapid growth, high yields and ease of manipulation, make them the premier choice for expression of non-glycosylated peptides and proteins. Innovative product classes such as antibody fragments or alternative binding molecules will further expand the use of microbial systems. Even more, novel, engineered production hosts and integrated technology platforms hold enormous potential for future applications. This review summarizes current applications and trends for development, production and analytical characterization of recombinant therapeutic proteins in microbial systems. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：164 / 186

页数：22

共 173 条

[61]

Bothmann H., Pluckthun A., The periplasmic Escherichia coli peptidylprolyl cis,trans-isomerase FkpA. I. Increased functional expression of antibody fragments with and without cis-prolines, J. Biol. Chem., 275, 22, pp. 17100-17105, (2000)

[62]

Joly J.C., Leung W.S., Swartz J.R., Overexpression of Escherichia coli oxidoreductases increases recombinant insulin-like growth factor-I accumulation, Proc. Natl. Acad. Sci. USA, 95, pp. 2773-2777, (1998)

[63]

Gemmill T.R., Trimble R.B., Overview of N- and O-linked oligosaccharide structures found in various yeast species, Biochim. Biophys. Acta., 1426, 2, pp. 227-237, (1999)

[64]

Daly R., Hearn M.T., Expression of heterologous proteins in Pichia pastoris: A useful experimental tool in protein engineering and production, J. Mol. Recogn., 18, pp. 119-138, (2005)

[65]

Cereghino J.L., Cregg J.M., Heterologous protein expression in the methylotrophic yeast Pichia pastoris, FEMS Microbiol. Rev., 24, 1, pp. 45-66, (2000)

[66]

Mendoza-Vega O., Sabatie J., Brown S.W., Industrial production of heterologous proteins by fed-batch cultures of the yeast Saccharomyces cerevisiae, FEMS Microbiol. Rev., 15, 4, pp. 369-410, (1994)

[67]

Kim K.Y., Kim H.E., Lee K.H., Han W., Yi M.J., Jeong J., Oh B.H., Two-promoter vector is highly efficient for overproduction of protein complexes, Protein Sci, 13, pp. 1698-1703, (2004)

[68]

Cannizzaro C., Valentinotti S., von Stockar U., Control of yeast fedbatch process through regulation of extracellular ethanol concentration, Bioprocess Biosyst. Eng., 26, 6, pp. 377-383, (2004)

[69]

Sonnleitner B., Kappeli O., Growth of Saccharomyces cerevisiae is controlled by its limited respiratory capacity: formulation and verification of a hypothesis, Biotechnol. Bioeng., 28, pp. 927-937, (1986)

[70]

Goodrick J.C., Xu M., Finnegan R., Schilling B.M., Schiavi S., Hoppe H., Wan N.C., High-level expression and stabilization of recombinant human chitinase produced in a continuous constitutive Pichia pastoris expression system, Biotechnol. Bioeng., 74, 6, pp. 492-497, (2001)

← 2 3 4 5 6 7 8 9 10 11 →