Sensitivity Analysis And Parameter Identification Of Nonlinear Hybrid Systems With Genetic Regulation For Glycerol Transport Mechanisms In Continuous Culture

Under the background of the bioconversion glycerol to1,3-propanediol by Klebsiella pneumoniae in continuous culture, we explore the sensitivity analysis and parameter identification of nonlinear hybrid systems for glycerol transport mechanisms, in which based on enzyme-catalytic kinetics on the reductive pathway, the repression of the dha regulon, PDOR and GDHt by3-hydroxypropionaldehy (3-HPA) are investigated. The main content in this paper is discussed as follows:1. With the glycerol metabolism by K. pneumoniae, considering that the transport mechanisms of1,3-PD and glycerol to across cell membrane are still unclear, under con-dition that1,3-Propanediol is assumed to pass the cell membrane by active transport and passive diffusion, we establish a modified fourteen-dimensional nonlinear hybrid dynamic system with genetic regulation for glycerol transport mechanisms, in which the existence, uniqueness, continuous dependence of solutions and the compactness of the solution set are discussed.2. Considering that too many parameters need to be identified would lead to high computational cost, we propose a novel global sensitivity analysis method to reduce pa-rameters to be identified. According to the definition of sensitivity index, parameters with higher values of sensitivity index need to be identified and parameters whose values are smaller than1would be considered as insensitive parameters. We propose a parameter identification model aiming at identifying the parameter with higher sensitivity and trans-port of glycerol, which takes the robustness index of the intracellular substance together with the relative error between the computational value and the experimental data for the extracellular substance as a performance index.3. Considering that it’s difficult to obtain analytical solution for identification mod-el, in which continuous and discrete variables were contained, we construct a parallel optimization algorithm to solve it. Finally, we obtained that the most reasonable trans-port mechanism of glycerol is passive diffusion coupling with active transport and the corresponding values of optimal parameters.