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毕赤酵母生物过程开发中的动力学

Dynamics in bioprocess development for Pichia pastoris.

作者信息

Spadiut Oliver, Herwig Christoph

机构信息

a Vienna University of Technology; Institute of Chemical Engineering ; Research Area Biochemical Engineering ; Vienna , Austria.

出版信息

Bioengineered. 2014;5(6):401-4. doi: 10.4161/bioe.36152. Epub 2014 Oct 30.

Abstract

Pichia pastoris is a widely used host organism for the recombinant production of proteins. It is attracting increasing interest for the production of biopharmaceuticals, due to its capability of performing posttranslational modifications. Traditionally, production processes with P. pastoris describe fed-batch processes based on feed forward regimes with a constant specific growth rate. However, this strategy does not consider physiological changes of the organism, bearing the risk of overfeeding and thus harming the cells. Recently, we introduced the specific substrate uptake rate as a novel physiological parameter to design fed-batch strategies for P. pastoris. We showed that by doing dynamic batch experiments strain specific parameters, which are needed to set up respective feeding profiles, can be easily determined. Furthermore we proved that dynamics during feeding directly affects productivity and product purity. Here, we sum up our findings regarding dynamics in bioprocess development for P. pastoris.

摘要

毕赤酵母是一种广泛用于重组生产蛋白质的宿主生物。由于其具有进行翻译后修饰的能力,它在生物制药生产中吸引了越来越多的关注。传统上,毕赤酵母的生产过程描述的是基于具有恒定比生长速率的前馈策略的补料分批过程。然而,这种策略没有考虑生物体的生理变化,存在过度投喂从而损害细胞的风险。最近,我们引入了比底物摄取速率作为一个新的生理参数来设计毕赤酵母的补料分批策略。我们表明,通过进行动态分批实验,可以轻松确定建立各自补料曲线所需的菌株特异性参数。此外,我们证明了补料过程中的动态直接影响生产率和产品纯度。在此,我们总结了关于毕赤酵母生物过程开发中动态变化的研究结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf2d/4601250/15d50b74621e/kbie-05-06-977163-g001.jpg

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