Model-guided in silico deletion of pntA gene predicts increased succinate production under anaerobic conditions in Escherichia coli

The production of succinic acid under anaerobic conditions in Escherichia coli faces a major obstacle of NADH limitation. Here, we used E. coli genome scale model and engineered in silico gene knockout strategies by deletion of the membrane-bound pyridine nucleotide transhydrogenase (pntA) using Minimization of Metabolic Adjustment (MOMA) algorithm with the OptFlux software platform. The metabolic role of this transhydrogenase during E. coli bio-catalysis in relation to succinic acid production has remained largely unspecified. This study informs other studies that the in silico deletion of this gene predicts increase succinic acid production in E. coli. The results indicate that the simulation of the mutant model lacking pntA/b1603 under anaerobic conditions with glucose as the substrate predicts increased succinate production that is twofold higher than the wild-type parent model. On the bases of these findings, we hypothesize that knocking out of the pntA transhydrogenase in E. coli might have resulted in a twofold increase in NADH availability, that catalyzes enhanced succinate production. These findings open up a novel model-driven biological inquiry in determining the underground metabolic function of the pntA/b1603 in NADPH and/or NADH regeneration in relation to succinic acid production in E. coli.