The authors declared they have no conflicts of interest.
Peak antibody production is associated with increased oxidative metabolism in an industrially relevant fed-batch CHO cell culture†
Article first published online: 4 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 110, Issue 7, pages 2013–2024, July 2013
How to Cite
Templeton, N., Dean, J., Reddy, P. and Young, J. D. (2013), Peak antibody production is associated with increased oxidative metabolism in an industrially relevant fed-batch CHO cell culture. Biotechnol. Bioeng., 110: 2013–2024. doi: 10.1002/bit.24858
- Issue published online: 25 MAY 2013
- Article first published online: 4 MAR 2013
- Accepted manuscript online: 4 FEB 2013 08:02AM EST
- Manuscript Accepted: 22 JAN 2013
- Manuscript Revised: 11 JAN 2013
- Manuscript Received: 26 JUL 2012
- Amgen, Inc.. Grant Number: 2010529686
- metabolic flux analysis (MFA);
- Chinese hamster ovary (CHO);
- lactate switch;
- antibody production;
- aerobic glycolysis
Cell metabolism can vary considerably over the course of a typical fed-batch antibody production process. However, the intracellular pathway alterations associated with various phases of growth and antibody production have yet to be fully elucidated using industrially relevant production hosts. Therefore, we performed 13C labeling experiments and metabolic flux analysis (MFA) to characterize CHO cell metabolism during four separate phases of a fed-batch culture designed to closely represent industrial process conditions. First, we found that peak specific growth rate was associated with high lactate production and minimal TCA cycling. Conversely, we found that lactate metabolism switched from net production to net consumption as the culture transitioned from peak growth to peak antibody production. During the peak antibody production phase, energy was primarily generated through oxidative phosphorylation, which was also associated with elevated oxidative pentose phosphate pathway (oxPPP) activity. Interestingly, as TCA cycling and antibody production reached their peaks, specific growth rate continued to diminish as the culture entered stationary phase. However, TCA cycling and oxPPP activity remained high even as viable cell density began to decline. Overall, we found that a highly oxidative state of metabolism corresponded with peak antibody production, whereas peak cell growth was characterized by a highly glycolytic metabolic state. Biotechnol. Bioeng. 2013; 110: 2013–2024. © 2013 Wiley Periodicals, Inc.