Metabolic Design of Macroscopic Models: Application to CHO cells

The aim of this paper is to present a systematic methodology to design macroscopic models for cell cultures based upon metabolic networks. The cell life is seen as a succession of phases. During each phase, a metabolic network represents the set of reactions occuring in the cell. Then, through the use of the Elementary Flux Modes, these metabolic networks are used to derive macroscopic reactions linking the extracellular substrates and products. On this basis, as many separate models are obtained as there are phases. Then, a complete model is obtained by smoothly switching from model to model. This is illustrated with batch cultures of Chinese Hamster Ovary (CHO) cells.