engleski

Model and global sensitivity analysis of E. coli central metabolism

This work provides analysis of kinetic behavior of the central metabolism of E. coli upon glucose impulse during the initial transients of 15 seconds. The analysis is based on the model derived from dynamic measurements of the key intracellular metabolites. Response of the central carbon metabolism (glycolysis and pentose phosphate pathway) is decoupled from the anabolic and TCA systems by the transient measurements of the cofactors and oxaloacetate concentrations. The kinetic parameters are initially estimated by the nonlinear Least Squares Method (with Marqardt minimization) and improved by several global optimization algorithms (simplex Nelder-Mead, Simulated Annealing and Differential Evolution). However, due to severe ill-conditioned problem, large errors in the estimates are inherently present. The focus of this research is to reveal which are the most important enzyme effectors, reflected by the corresponding kinetic parameters, responsible for modeling of the input-output fluxes of the central metabolism. Applied is the Fou-rier Amplitude Sensitivity Test (FAST) for global sensitivity analysis. Identified are the key ki-netic parameters responsible for the following fluxes: phosphotransferase system (PTS), nucleo-tide biosynthesis and pyruvate to biomass. The results could be potentially applicable for under-standing of the metabolism regulation and for rational application of genetic engineering.

E.coli; central metabolism; global sensitivity

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