Empirical approaches for media development in the biotech industry, while effective are limited to the discovery of local optima in media composition. In comparison, constraint-based analysis of metabolic networks offers a facile and rational approach for global optimization of cell culture media as demonstrated in this study. We initially developed a metabolic model consisting of 46 metabolites and 78 fluxes, which primarily represented glycolysis, amino-acid metabolism, TCA cycle, biomass and antibody production. A linear programming-based method was then used to optimize for production of cellular biomass. Based on the model predictions for amino-acid consumption, the relative levels of the various amino acids were adjusted to create a novel feed medium that yielded a 40% increase in the total viable cell-count by day 6 of fed-batch cell culture. As a continuation of this effort, a larger model was subsequently created that included additional pathways such as lipid, cholesterol and nucleotide metabolism.

Improvements in mammalian cell culture by use of metabolic flux analysis

243rd National Meeting (2012)

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