Abstract:[Objective] The aim of the present study was to find key factors of arginine metabolism on the stress tolerance. [Methods] Arginine metabolism was switched by argininosuccinate synthase (ASS) or argininosuccinate lyase (ASL) overexpression in L. lactis NZ9000 to enhance the stress tolerance. [Results] The recombinant strains exhibited higher growth performance, viability and fermentation performance compared with the control strain under environmental stresses. Analysis of the physiological data showed that the recombinant cells exhibited higher intracellular pH, intracellular NH4+ and ATP content, and H+-ATPase activity under acid stress, and the content of amino acid in arginine deiminase (ADI) pathway was significantly higher than the control strain. Further transcriptional analysis showed that the expression of the genes related to aspartate synthesis and arginine catabolism were up-regulated. [Conclusion] These results suggest that ASS or ASL overexpression in L. lactis NZ9000 can enhance arginine metabolism flux and up-regulated arginine metabolism flux improve the multiple-stress tolerance of cells. As arginine synthesis pathway widely exists in various kinds of microorganisms, results presented in this study provide new idea to enhance stress tolerance of tons of microorganisms especially industrial strains.