文献类型：期刊文献

英文题名：Physiological responses of Chinese hamster ovary cells to a productivity-enhancing yeast extract

作者：Hu, Dongdong[1];Zhao, Liang[1];Wang, Jiaqi[1];Fan, Li[1];Liu, Xuping[1];Wang, Haibin[2];Tan, Wen-Song[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Box 309,130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Zhejiang Hisun Pharmaceut Co Ltd, Hangzhou 311404, Zhejiang, Peoples R China

年份：2018

卷号：126

期号：5

起止页码：636

外文期刊名：JOURNAL OF BIOSCIENCE AND BIOENGINEERING

收录：;EI(收录号：20182205252111);WOS:【SCI-EXPANDED(收录号:WOS:000450375400014)】；

基金：This work was supported by the National Natural Science Foundation of China (Nos. 21206040 and 21406066), the National Science and Technology Major Project (No. 2013ZX10004003-003-003), the Fundamental Research Funds for the Central Universities (No. 22221818014), and the National High Technology Research and Development Program of China (863 Program) (No. 2012AA02A303). The authors have declared no conflict of interest.

语种：英文

外文关键词：Chinese hamster ovary cells; Yeast extract; Fc-fusion protein; Specific productivity; Amino acid metabolism; Energy charge

摘要：Hydrolysates play important roles in enhancing the productivity of recombinant proteins in mammalian cell cultures. Lacking of detailed understanding of the mechanisms, hydrolysate is commonly regarded as an unstable factor which should be used with cautions. A yeast extract (YE) was approved to improve the Fc-fusion protein productivity in a recombinant Chinese hamster ovary (CHO) cell line. To elucidate the responses of cells to hydrolysates, we further elaborate their physiological changes during the processes in the presence and absence of YE. Firstly, cell sizes and the cellular components including dry cell weight, cellular fatty acid, and total cellular protein were increased in the presence of YE. Then, by comparing the extracellular and intracellular concentrations of the main metabolites and their consumption rates, we excluded the possibility of nutrient depletion in the absence of YE and observed a distinct improvement on the net consumption rates of metabolites in the presence of YE. Furthermore, the increase on the contents of intracellular nucleotides illustrated an abundance of the nucleic acid precursors and energy charge for recombinant protein synthesis in the presence of YE. In conclusion, this study systematically elucidated YE enhanced cell mass and capacity, activated substrate and energy metabolism of cells in addition to a boost in product synthesis process. The findings provide valuable information for process optimization and cell engineering. (C) 2018, The Society for Biotechnology, Japan. All rights reserved.