NDLI: High-temperature cultivation of recombinant Pichia pastorisincreases endoplasmic reticulum stress and decreases production of human interleukin-10

Content Provider	Springer Nature : BioMed Central
Author	Zhong, Yongjun Yang, Lu Guo, Yugang Fang, Fang Wang, Dong Li, Rui Jiang, Ming Kang, Wenyao Ma, Jiajia Sun, Jie Xiao, Weihua
Abstract	Background The yeast Pichia pastoris (P. pastoris) has become a popular `cell factory' for producing heterologous proteins, but production widely varies among proteins. Cultivation temperature is frequently reported to significantly affect protein production; however, the underlying mechanisms of this effect remain unclear. Results A P. pastoris strain expressing recombinant human interleukin-10 (rhIL-10) under the control of the AOX1 promoter was used as the model in this study. This system shows high-yield rhIL-10 production with prolonged methanol-induction times when cultured at 20°C but low-yield rhIL-10 production and higher cell death rates when cultured at 30°C. Further investigation showed that G3-pro-rhIL10, an immature form of rhIL-10 that contains the glycosylation-modified signal peptide, remained in the ER for a prolonged period at 30°C. The retention resulted in higher ER stress levels that were accompanied by increased ROS production, Ca2+ leakage, ER-containing autophagosomes, shortened cortical ER length and compromised induction of the unfolded protein response (UPR). In contrast, G3-pro-rhIL10 was quickly processed and eliminated from the ER at 20°C, resulting in a lower level of ER stress and improved rhIL-10 production. Conclusions High-temperature cultivation of an rhIL-10 expression strain leads to prolonged retention of immature G3-pro-rhIL10 in ER, causing higher ER stress levels and thus greater yeast cell death rates and lower production of rhIL-10.
Related Links	https://microbialcellfactories.biomedcentral.com/counter/pdf/10.1186/s12934-014-0163-7.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14752859
DOI	10.1186/s12934-014-0163-7
Journal	Microbial Cell Factories
Issue Number	1
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2014-11-26
Access Restriction	Open
Subject Keyword	Applied Microbiology Biotechnology Microbiology Microbial Genetics and Genomics Enzymology Genetic Engineering High-temperature cultivation Misfolded protein ER stress Unfolded protein response ER-phagy Pichia pastoris
Content Type	Text
Resource Type	Article
Subject	Applied Microbiology and Biotechnology Bioengineering Biotechnology
Journal Impact Factor	4.3/2023
5-Year Journal Impact Factor	5.5/2023

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