Modeling and Computer Simulation for the Main Metabolism

Modeling of the main metabolic pathways such as glycolysis, TCA cycle, pentose phosphate (PP) pathway, and anaplerotic pathways is considered, where the fluxes obtained by computer simulation can be used to compute the specific ATP production rate, the specific CO2 production rate, and the specific NAD(P)H production rate. The specific ATP production rate thus computed can be used for the estimation of the specific growth rate. The model can be further extended for catabolite regulation by incorporating the effects of transcription factors such as Cra and cAMP-Crp, where acetate overflow metabolism and co-consumption of multiple sugars can be clarified by this modeling approach. Modeling for anaerobic fermentation is also considered, where aerobic/ anaerobic switch can be made by incorporation of the roles of ArcA/B and Fnr. Modeling for NH3 assimilation pathways is then considered, where this may be combined with the main metabolism to simulate nitrogen regulation at various C/N ratios. Finally, amino acid synthetic pathways are considered for lysine production.

Keywords: Modeling, kinetics, computer simulation, dynamic simulation, gene knockout mutant, Escherichia coli, catabolite regulation, co-consumption of multiple carbon sources, nitrogen metabolism, anaerobic fermentation, transcription factors, lysine fermentation.