Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile

被引:27
作者
Jenzsch, Marco
Gnoth, Stefan
Kleinschmidt, Martin
Simutis, Rimvydas
Luebbert, Andreas
机构
[1] Univ Halle Wittenberg, Zentrum Bioverfahrenstech, D-06120 Halle, Germany
[2] Probiodrug AG, Prot Res, D-06120 Halle, Germany
[3] Kaunas Univ Technol, Inst Automat & Control Syst, Kaunas, Lithuania
关键词
PAT E. coli fed batch; reproducibility; recombinant proteins;
D O I
10.1007/s00449-006-0080-1
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
In industry Escherichia coli is the preferred host system for the heterologous biosynthesis of therapeutic proteins that do not need posttranslational modifications. In this report, the development of a robust high-cell-density fed-batch procedure for the efficient production of a therapeutic hormone is described. The strategy is to guide the process along a predefined profile of the total biomass that was derived from a given specific growth rate profile. This profile might have been built upon experience or derived from numerical process optimization. A surprisingly simple adaptive procedure correcting for deviations from the desired path was developed. In this way the batch-to-batch reproducibility can be drastically improved as compared to the process control strategies typically applied in industry. This applies not only to the biomass but, as the results clearly show, to the product titer also.
引用
收藏
页码:315 / 321
页数:7
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