[Background]Lactococcus lactis is a representative strain in the food industry. The molecular mechanism of L. lactis responding to environmental factors and the metabolic regulation through the two-component system is of great importance to the fermented food and the probiotics industries. [Objective] This study aimed to explore the effect of two-component system of L. lactis on aerobic respiration metabolism, and was expected to supply a new direction for adaptive metabolism in lactic acid bacteria. [Methods] The domainof sensor histidine kinases and response regulatory factor as well as the function of the two-component system in L. lactis was systematically analyzed using bioinformatics methods. The correlations between two-component system and aerobic respiration were calculated and further verified by transcriptional expression and untargeted metabolomics. [Results] The protein-protein interaction network of the representative L. lactis strain NZ9000 showed that the key connection point between the two-component system and pyruvate metabolism in the network was pyruvate-ferredoxin oxidoreductase (nifJ). At different growth stages, the transcriptional expression of the two-componentsystem in L. lactis NZ9000 changed significantly in the lag period. Compared with the anaerobic culture, the transcriptional expression of the two-component system in L. lactis NZ9000 cultivated under aerobic culture and aerobic respiratory culture was down-regulated. The two-component system participated in oxidative stress and heme stress in lactic acid bacteria. [Conclusion] To identify the two-component system and metabolic pathway of Lactococcus lactis involved in aerobic respiration. It can improve the survival rate and competitiveness of starters and probiotics.
