Metabolic flux distribution and mathematical models for dynamic simulation of carbon metabolism in Escherichia coli

Abstract

A simple model was build for the metabolic flux determination based on published articles. A method for metabolic flux determination by carbon labeling experiments was described and developed here in the first part of this study that allows mathematical description relating the measured quantities and the intracellular fluxes. The described method was used to investigate the central carbon metabolism of Escherichia coli. In the second part of this study, computer simulation was made to study the dynamics of the intracellular metabolite concentrations in E. coli in particular for the glycolysis and pentosephosphate pathway based on the kinetic rate equations. The model successfully simulates the main features of the time course without alteration of the experimentally determined parameters. After simulation starts, the intracellular concentrations of ATP, PEP, PYR, G6P, F6P, NAD and 3PG decreased while FDP, 6PG, S7P, E4P AMP, GAP, ADP, NADH and NADPH increased for wild E. coli. These simulation results were also partly verified by experimental results.

Key words: Metabolic flux, metabolite concentration, computer simulation, optimization technique, parameters.