Overcoming Toxicity Barriers for Boosting Nisin Synthesis in <i>Lactococcus lactis</i> Strain via Adaptive Laboratory Evolution

ABSTRACT Nisin is a widely used and safe bio‐antibacterial substance in food industries. The production of nisin in microorganisms is hindered by its toxic effects on the strains, preventing efficient synthesis. To enhance the nisin production ability of Lactococcus lactis CICC 6242, adaptive laboratory evolution against nisin was employed in this study. The evolved strains with improved nisin tolerance and production capacity were obtained. The culture of the evolved strains exhibited an inhibitory effect on Staphylococcus aureus equivalent from 2535 IU/mL to 3071 IU/mL of nisin, which was increased by approximately 21.10% compared to that of the wild‐type strain. Furthermore, the cellular structure of the evolved strains was observed to be more saturated, with a smoother and more homogeneous surface under stress conditions. The combination analysis of metabonomics, transcriptomics and genomics found that the enhanced production of nisin in the evolved strains was primarily attributable to the augmented expression of membrane structure and transporter genes in the transcriptome, as well as the elevated content of cell surface components and compounds involved in energy metabolism in the metabolome.