文献类型：期刊文献

英文题名：Insight into the roles of tyrosine on rCHO cell performance in fed-batch cultures

作者：Tang, Hongping[1];Zhang, Xintao[1];Zhang, Weijian[1];Fan, Li[1];Wang, Haibin[2];Tan, Wen-Song[1];Zhao, Liang[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Zhejiang Hisun Pharmaceut Co Ltd, Hangzhou 311404, Zhejiang, Peoples R China

年份：2019

卷号：103

期号：16

起止页码：6483

外文期刊名：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY

收录：;EI(收录号：20192507073157);WOS:【SCI-EXPANDED(收录号:WOS:000477927800008)】；

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

语种：英文

外文关键词：Chinese hamster ovary cells; Tyrosine; Cell death; Autophagy; Culture pH

摘要：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 (q(mAb)) 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.