Addressing the Bottlenecks in the Production of Propionic Acid via Kinetic Modelling and Metabolic Control Analysis
In microorganisms, propionic acid is mainly produced via the acrylate and dicarboxylate pathway. In a previous study, a recombinant E.coli engineered with genes from Clostridium propionicum produced a low propionate titre (3.2mM), despite high precursor (lactate) formation of (0.9g/g of glucose). Metabolic regulation of the pathway enzymes was speculated to be a key factor impeding propionate production. Kinetic modelling was undertaken to capture the reaction dynamics and intermediate concentration by varying the enzyme activities. The model was fitted with experimental propionic acid formation data from previous study. The model was fine-tuned through enzyme activity measurements and related kinetic parameters. The optimal enzyme activity ratios required for the complete conversion of the recombinant lactate flux to propionate were predicted using the validated model.
Index terms - Kinetic modelling, Propionic acid, E.coli, Acrylate pathway, Lactate.