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Enhanced porcine interferon-alpha production by recombinant Pichia pastoris with a combinational control strategy of low induction temperature and high dissolved oxygen concentration

文献类型： 外文期刊

作者： Jin, Hu 1 ; Liu, Guoqiang 1 ; Ye, Xiaofei 2 ; Duan, Zuoying 1 ; Li, Zhen 2 ; Shi, Zhongping 1 ;

作者机构： 1.Jiangnan Univ, Key Lab Ind Biotechnol, Minist Educ, Sch Biotechnol, Wuxi 214122, Peoples R China

2.Shanghai Acad Agr Sci, Anim Husb & Vet Res Inst, Shanghai Municipal Key Lab Agri Genet & Breeding, Shanghai 201106, Peoples R China

关键词： Induction;Metabolic analysis;On-line fed-batch;Optimization;Pichia pastoris;Recombinant protein production

期刊名称：BIOCHEMICAL ENGINEERING JOURNAL （ 影响因子：3.978； 五年影响因子：4.084 ）

ISSN： 1369-703X

年卷期： 2010 年 52 卷 1 期

页码：

收录情况： SCI

摘要： Porcine interferon-alpha (pIFN-alpha) production by recombinant Piano postoris with standard induction strategy at 30 degrees C often suffers problems such as low antiviral activity, long cells adaptation period, etc. To solve these problems, a combinational induction strategy by simultaneously controlling induction temperature at 20 degrees C and dissolved oxygen concentration (DO) over 50% was proposed and the relevant fermentation runs were conducted in a 51 bioreactor. With this control strategy, pIFN-alpha antiviral activity could be continuously enhanced and eventually reached a level of 3.62 x 10(7) IU/ml, which was about 16-fold of the maximum obtained when induction was clone at 20 degrees C but without DO control, and more than 100-fold of the maximum obtained with the standard induction strategy at 30 degrees C. The novel control strategy could enhance alcohol oxidase (AOX) activity and relieve oxygen supply limitation in oxidative phosphorylation reaction to accelerate ATP regeneration simultaneously. As a result, the metabolic flux towards pIFN-alpha synthesis was enhanced and the adaptation period was shortened, enabling the entire system to be operated in a most efficient way. (C) 2010 Elsevier B.V. All rights reserved.

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