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Improvement of ATP regeneration efficiency and operation stability in porcine interferon-α production by Pichia pastoris under lower induction temperature

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Abstract

The performance of traditional heterologous protein production by Pichia pastoris with methanol induction at 30 °C is poor, characterized by low ATP regeneration rate and weak operation stability. A low temperature induction strategy at 20 °C was thus adopted for efficient porcine interferon-α production in a 10 L fermentor. With the strategy, maximal methanol tolerance level could reach about 40 g/L to effectively deal with methanol concentration variations, so that the complicated on-line methanol measurement system could be eliminated. Moreover, metabolic analysis based on multiple state-variables measurements indicated that pIFN-α antiviral activity enhancement profited from the formation of an efficient ATP regeneration system at 20 °C induction. Compared to the induction strategy at 30 °C, the proposed strategy increased the ATP regeneration rate by 49–66%, the maximal pIFN-α antiviral activity was enhanced about 20-fold and reached a higher level of 1.5×106 IU/mL.

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Authors and Affiliations

  1. Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Minjie Gao, Jianrong Wu, Zhiyong Zheng, Zhongping Shi & Xiaobei Zhan

  2. Animal Husbandry and Veterinary Research Institute, Shanghai Academy of Agricultural Science, Shanghai Municipal Key Laboratory of Agri-Genetics and Breeding, Shanghai, 201106, China

    Shijuan Dong & Ruisong Yu

Authors
  1. Minjie Gao
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  2. Shijuan Dong
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  3. Ruisong Yu
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  4. Jianrong Wu
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  5. Zhiyong Zheng
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  6. Zhongping Shi
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  7. Xiaobei Zhan
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Correspondence to Zhongping Shi.

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Gao, M., Dong, S., Yu, R. et al. Improvement of ATP regeneration efficiency and operation stability in porcine interferon-α production by Pichia pastoris under lower induction temperature. Korean J. Chem. Eng. 28, 1412–1419 (2011). https://doi.org/10.1007/s11814-010-0527-6

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  • DOI: https://doi.org/10.1007/s11814-010-0527-6

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