Despite significant investments in research and development in the past decades, relatively little is known about intracellular metabolism of CHO cells in cell culture. In this work, the metabolism of CHO cells was studied in detail during a fed-batch fermentation. Metabolism was characterized by measured extracellular uptake and excretion rates of metabolites combined with a detailed metabolic network model for CHO cells. To obtain additional information 13C-tracers were applied and labeling of intracellular metabolites was measured using mass spectrometry (GC-MS). Fluxes were quantified using non-stationary 13C-metabolic flux analysis. The flux results revealed significant rewiring of intracellular metabolic fluxes in the transition from growth phase to stationary phase, including changes in energy metabolism and redox metabolism. The results that we present provide a solid foundation for future studies of CHO cell metabolism for applications such as cell line development and medium optimization for high-titer production of recombinant proteins.

Metabolic flux analysis of CHO cells in fed-batch culture

243rd National Meeting (2012)

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