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

Mauro Torres, JULIO ANDRES BERRIOS ARAYA, Yandi Rigual, Yesenia Latorre, Mauricio Vergara, Alan J. Dickson, CLAUDIA VICTORIA ALTAMIRANO GOMEZ

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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
DOIs
StatePublished - 21 Sep 2019

Keywords

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

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