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Zusammenfassung:
Complex pharmaceutical glycoproteins are produced in mammalian cell lines. Efficient
industrial production typically requires optimization of productivities and process
conditions for the individual producer cell line. In that context system biology approaches,
such as stationary metabolic flux analysis may provide a powerful tool for
optimizing the production process. In addition this may allow for identification of superior
targets for cell engineering to further enhance the yields.
Cell metabolism and alpha1-antitrypsin (AAT) productivity was analyzed for different
steady states in continuous culture. We demonstrate that the glucose to glutamine
ratio in the feed medium have a significant impact on productivity. Depending on particular
glucose/glutamine ratios and dilution rates cell specific AAT productivity was
found to be up to 50% enhanced comparing different steady states.