Dynamics Analysis and Prediction of Genetic Regulation in Glycerol Metabolic Network via Structural Kinetic Modelling

Glycerol can be biologically converted to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae . In the synthesis pathway of 1,3-PD, the accumulation of an intermediary metabolite 3-hydroxypropionaldehyde (3-HPA) would cause an irreversible cessation of the dynamic system. Genetic manipulation on the key enzymes which control the formation rate and consumption rate of 3-HPA would decrease the accumulation of 3-HPA, resulting in nonlinear regulation on the dynamic system. The interest of this work is to focus on analyzing the influence of 3-HPA inhibition on the stability of the dynamic system. Due to the lack of intracellular knowledge, structural kinetic modelling is applied. On the basis of statistical account of the dynamical capabilities of the system in the parameter space, we conclude that, under weak or no inhibition to the reaction of 3-HPA consumption, the system is much easier to obtain a stable state, whereas strong inhibition to its formation is in favor of stabilizing the system. In addition, the existence of Hopf bifurcation in this system is also verified. The obtained results are helpful for deeply understanding the metabolic and genetic regulations of glycerol fermentation by Klebsiella pneumoniae .