Metabolic flux analysis during galactose and lactate co-consumption reveals enhanced energy metabolism in continuous CHO cell cultures

Mauro Torres, Julio Berrios, Yandi Rigual, Yesenia Latorre, Mauricio Vergara, Alan J. Dickson, Claudia Altamirano*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Chinese Hamster Ovary (CHO) cells are the main expression system for production of therapeutic recombinant (r-) proteins. The increased demand for these therapeutics has boosted the development of more robust production processes. Use of optimised feed/media has dramatically improved the performance of CHO cells in culture. However, such progress in biomass synthesis and r-protein production often come with an increased accumulation of lactate. In this study, we present a combined feeding strategy that uses galactose and lactate to replace glucose in CHO cell cultures. Replacement of glucose by galactose and lactate sustained cell growth and r-protein production in CHO cells. This strategy supported a better-balanced and more efficient metabolism, observed by an overall decreased consumption of carbon sources and amino acids, associated with an increased ATP production per C-mol consumed. Our results provide new insights of CHO cell metabolism in glucose-free media based on galactose and lactate.

Original languageEnglish
Pages (from-to)201-211
Number of pages11
JournalChemical Engineering Science
Volume205
Early online date2 May 2019
DOIs
Publication statusPublished - 21 Sept 2019

Keywords

  • Biochemical engineering
  • Biopharmaceuticals
  • Bioprocessing
  • Lactate
  • Metabolic flux analysis
  • Metabolism modelling

Research Beacons, Institutes and Platforms

  • Manchester Institute of Biotechnology

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