Reconstruction and validation of genome-scale metabolic model of L. lactis subsp. lactis NCDO 2118 and in silico analysis for succinate and Gamma-aminobutyric acid overproduction

Abstract Non-dairy Lactococcus lactis subsp. lactis NCDO 2118 is well known for its Gamma-aminobutyric acid (GABA) producing capability. In this study, genome-scale metabolic model of Lactococcus lactis subsp. lactis NCDO 2118 covering 62 pathways and consisting of 1084 genes, 965 reactions, and 864 metabolites was reconstructed. The validation process was performed using various types of physiological data. Validated model could predict growth rates on different defined media similar to the experimental data. Also, flux distribution through metabolic pathways was simulated by the resultant model, which was similar to experimental flux distribution data. The final model named iOA1084. After model validation, GABA production under normal and high glutamate uptake rates was investigated using flux balance analysis (FBA). iOA1084 predicts that an increase in glutamate uptake rate results in a high GABA production rate, which is a proton consuming reaction. This depletion of cytosolic proton might result in changing ATP synthase reaction from ATP consumption to ATP production. Also, iOA1084 showed an enhanced succinate production rate in aerobic conditions. Further in silico analysis showed that bacterium might use a different pathway from the citric acid cycle to produce succinate. iOA1084 suggested that knocking out of arginine and glycine exchange reactions could result in more succinate production.