Comparison of the productivity of a new human cell line in different steady states of continuous cultivations using MFA

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