Computational prediction of impact of rerouting the carbon flux in metabolic pathway on cell growth and nisin production by Lactococcus lactis

The detrimental effect of a low pH due to the accumulation of lactate on cell growth and nisin production by Lactococcus lactis is well known. To avoid such an inhibitory effect of lactate and to enhance nisin production, a new strategy by rerouting the carbon flux was considered. This strategy will be conducted in two ways: (i) rerouting the carbon flux to ethanol, or (ii) rerouting the carbon flux to alanine. To confirm the feasibility of both compounds as targets to reroute the carbon flux, their inhibitory effects on cell growth and nisin production were investigated. For this purpose, a mathematical model was developed to investigate the nisin production during the cultivation of L. lactis subsp. lactis ATCC11454 with addition of the compounds. The constructed model then was applied to estimate the optimum redirection ratio of the carbon flux to ethanol. The model described that nisin production with rerouting the carbon flux to ethanol was 1.7 times higher than that without rerouting the carbon flux. Investigation of inhibitory effect of alanine was also carried out and the result confirmed that alanine gave no significant inhibitory effect on both cell growth and nisin production. Based on the calculation, the optimum of nisin production was estimated twice higher than that without rerouting the carbon flux. The proposed model here provided a reasonable description to estimate and to evaluate quantitatively the feasibility of rerouting the carbon flux to ethanol or alanine to achieve a high nisin production.