Parameter estimation in kinetic models for large scale biotechnological systems with advanced mathematical programming techniques (original) (raw)
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Bio Systems, 2010
The construction of dynamic metabolic models at reaction network level requires the use of mechanistic enzymatic rate equations that comprise a large number of parameters. The lack of knowledge on these equations and the difficulty in the experimental identification of their associated parameters, represent nowadays the limiting factor in the construction of such models. In this study, we compare four alternative modeling approaches based on Michaelis–Menten kinetics for the bi-molecular reactions and different types of simplified rate equations for the remaining reactions (generalized mass action, convenience kinetics, lin-log and power-law). Using the mechanistic model for Escherichia coli central carbon metabolism as a benchmark, we investigate the alternative modeling approaches through comparative simulations analyses. The good dynamic behavior and the powerful predictive capabilities obtained using the hybrid model composed of Michaelis–Menten and the approximate lin-log kinetics indicate that this is a possible suitable approach to model complex large-scale networks where the exact rate laws are unknown.
Model Identification, Parameter Estimation, and Dynamic Flux Analysis of E. coli Central Metabolism
Chemical and Biochemical Engineering Quarterly
In this work are applied three global optimisation algorithms for adaptation of the mathematical model of the central metabolism of Escherichia coli to data obtained in the experiment with response to glucose impulse. Applied is the adaptive simplex method by Nelder-Mead, evolutionary algorithms of differential evolution, and simulated annealing. The original model has been modified by the following steps: closure of Entner- -Doudoroff pathway with pyruvate balance, introduction of phosphoenolpyruavate carboxylase and carboxykinase reactions in the balance of phosphoenolypyravate, account for loss of pyruvate in biomass synthesis, change in kinetic rate expressions for several enzymes, and partial re-estimation of the kinetic parameters by the global optimisation algorithms. The modified model correctly predicts observed oscillatory response to glucose impulse in concentrations of pyruvate and D-ribose-5-phosphate. To discern metabolic control, evaluated are dynamic intracellular fl...