The sensitivity and significance analysis of parameters in the model of pH regulation on lactic acid production by Lactobacillus bulgaricus

Background: The excessive production of lactic acid by L. bulgaricus during yogurt storage is a phenomenon we are always tried to prevent. The methods used in industry either control the post-acidification inefficiently or kill the probiotics in yogurt. Genetic methods of changing the activity of one enzyme related to lactic acid metabolism make the bacteria short of energy to growth, although they are efficient ways in controlling lactic acid production. Results: A model of pH-induced promoter regulation on the production of lactic acid by L. bulgaricus was built. The modelled lactic acid metabolism without pH-induced promoter regulation fitted well with wild type L. bulgaricus (R ² _LAC = 0.943, R ² _LA = 0.942). Both the local sensitivity analysis and Sobol sensitivity analysis indicated parameters T _max , GR, K _LR , S, V ₀ , V ₁ and d _LR were sensitive. In order to guide the future biology experiments, three adjustable parameters, K _LR , V ₀ and V ₁ , were chosen for further simulations. V ₀ had little effect on lactic acid production if the pH-induced promoter could be well induced when pH decreased to its threshold. K _LR and V ₁ both exhibited great influence on the producing of lactic acid. Conclusions: The proposed method of introducing a pH-induced promoter to regulate a repressor gene could restrain the synthesis of lactic acid if an appropriate strength of promoter and/or an appropriate strength of ribosome binding sequence (RBS) in lacR gene has been designed.