Verónica S. Martínez and Stefanie Dietmair contributed equally to this work.
Communication to the Editor
Flux balance analysis of CHO cells before and after a metabolic switch from lactate production to consumption†
Article first published online: 5 NOV 2012
Copyright © 2012 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 110, Issue 2, pages 660–666, February 2013
How to Cite
Martínez, V. S., Dietmair, S., Quek, L.-E., Hodson, M. P., Gray, P. and Nielsen, L. K. (2013), Flux balance analysis of CHO cells before and after a metabolic switch from lactate production to consumption. Biotechnol. Bioeng., 110: 660–666. doi: 10.1002/bit.24728
- Issue published online: 20 DEC 2012
- Article first published online: 5 NOV 2012
- Accepted manuscript online: 18 SEP 2012 09:09AM EST
- Manuscript Accepted: 7 SEP 2012
- Manuscript Revised: 16 AUG 2012
- Manuscript Received: 9 FEB 2012
- flux balance analysis;
- CHO cells;
- metabolic switch;
- lactate metabolism;
- energy metabolism
Mammalian cell cultures typically exhibit an energy inefficient phenotype characterized by the consumption of large quantities of glucose and the concomitant production of large quantities of lactate. Under certain conditions, mammalian cells can switch to a more energy efficient state during which lactate is consumed. Using a metabolic model derived from a mouse genome scale model we performed flux balance analysis of Chinese hamster ovary cells before and after a metabolic switch from lactate production (in the presence of glucose) to lactate consumption (after glucose depletion). Despite a residual degree of freedom after accounting for measurements, the calculated flux ranges and associated errors were narrow enough to enable investigation of metabolic changes across the metabolic switch. Surprisingly, the fluxes through the lower part of the TCA cycle from oxoglutarate to malate were very similar (around 60 µmol/gDW/h) for both phases. A detailed analysis of the energy metabolism showed that cells consuming lactate have an energy efficiency (total ATP produced per total C-mol substrate consumed) six times greater than lactate producing cells. Biotechnol. Bioeng. 2013; 110: 660–666. © 2012 Wiley Periodicals, Inc.