Insight into the roles of tyrosine on rCHO cell performance in fed-batch cultures

  • Hongping Tang
  • Xintao Zhang
  • Weijian Zhang
  • Li Fan
  • Haibin Wang
  • Wen-Song TanEmail author
  • Liang ZhaoEmail author
Biotechnological products and process engineering


Tyrosine (Tyr), as one of the least soluble amino acids, is essential to monoclonal antibody (mAb) production in recombinant Chinese hamster ovary (rCHO) cell cultures since its roles on maintaining the specific productivity (qmAb) and avoiding Tyr sequence variants. To understand the effects of Tyr on cell performance and its underlying mechanisms, rCHO cell–producing mAbs were cultivated at various cumulative Tyr addition concentrations (0.6 to 5.5 mM) in fed-batch processes. Low Tyr concentrations gave a much lower peak viable cell density (VCD) during the growth phase and also induced rapid cell death and pH decrease during the production phase, resulting in a low efficient fed-batch process. Autophagy was initiated following the inhibition of mTOR under the Tyr starvation condition. Excessive autophagy subsequently induced autophagic cell death, which was found as the major type of cell death in this study. Additionally, the results obtained here demonstrate that the decrease in culture pH under the Tyr starvation condition was associated with the autophagy and such pH drop might be attributed to the lysosome acidification and cell lysis.


Chinese hamster ovary cells Tyrosine Cell death Autophagy Culture pH 


Funding information

This work was supported by the Fundamental Research Funds for the Central Universities (No. 22221818014).

Compliance with ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

253_2019_9921_MOESM1_ESM.pdf (294 kb)
ESM 1 (PDF 293 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiChina
  2. 2.Zhejiang Hisun Pharmaceutical Co., Ltd.ZhejiangChina

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