Effective and stable porcine interferon-alpha production by Pichia pastoris fed-batch cultivation with multi-variables clustering and analysis

文献类型： 外文期刊

第一作者： Jin, Hu

作者： Jin, Hu;Gao, Mingjie;Duan, Zuoying;Zheng, Zhiyong;Shi, Zhongping;Yu, Ruisong;Dong, Shijuan;Zhu, Yumin;Li, Zhen

作者机构：

关键词： Fed-batch culture;Multi-variables clustering;Oxygen uptake rate (OUR);Pichia pastoris;Porcine interferon-alpha expression

期刊名称：BIOPROCESS AND BIOSYSTEMS ENGINEERING （ 影响因子：3.21； 五年影响因子：2.97 ）

ISSN： 1615-7591

年卷期： 2010 年 33 卷 4 期

页码：

收录情况： SCI

摘要： Efficient porcine interferon-alpha (pIFN-alpha) expression in high density recombinant Pichia pastoris cultivation was achieved in a 5 l bench-scaled bioreactor. The results indicated that a high and stable oxygen uptake rate (OUR) during induction phase was closely related with pIFN-alpha production efficiency. The multi-variables clustering and analysis results showed that the achievement of a high and stable OUR relied on a higher glycerol consumption rate during fed-batch culture phase and a moderate methanol level (around 10 g/l) during induction phase. In the high and stable OUR environments (200-300 mmol/l/h), the highest pIFN-alpha antiviral activity could reach a level of 6.7 x 10(6) IU/ml, which was more than 10-300-folds higher than those obtained at lower OUR (80-200 mmol/l/h) using the same bioreactor and those obtained in shaking flasks. Clustering and analysis of the specific growth and glycerol consumption rates data during culture phase could detect the ill fermentation state at early stage, potentially provided a simple and effective fault alarming/diagnosis method for the achievement of stable pIFN-alpha production.

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