碳代谢导致的产酸积累是促使微生物细胞活性降低的关键因素，但目前尚缺乏基于对抗酸元器件生理调控机制解析的高效筛选及靶向控制策略。本项目以乳酸乳球菌NZ9000为模式菌株，在整合前期研究中抗酸胁迫生理调控及组学数据的基础上，筛选具有典型作用机制的新型抗酸元器件，并通过对元器件间的互作关系分析，确定协同作用的抗酸元器件装配方案。通过基因组代谢调控模型优化，应用流量平衡分析对抗酸元器件作用下的细胞生理特性进行效能预测，并根据最终拟合的抗酸元器件装配方案对原始菌株进行分子改造，构建抗酸胁迫预测突变株。通过原始菌株与突变株细胞生理活性的考察，验证并确定具有显著抗酸效果且对菌体自身代谢微扰动的抗酸元器件及其组装模块。在此基础上，结合菌株间的细胞生理学差异，解析抗酸元器件在不同微生物种群间的普适性作用机制，为工业微生物家族成员抗酸胁迫生理功能的强化奠定坚实的理论基础。

The acid accumulation caused by carbon metabolism is the key factor to reduce physiological activity of microorganisms. However, at present, it is still short of efficient screening and targeting control strategies based on the analysis of regulatory mechanism of anti-acid components. In this study, Lactococcus lactis NZ9000 is used as the type strain, and novel anti-acid components with typical function will be screened according to previous physiological regulation and omics data. Meanwhile, assembly solutions with different anti-acid components will be chosen after their interaction evaluation. After the genome-scale metabolic regulation model reconstruction, the flux balance analysis will be applied to predict the effect of anti-acid components on cell's physiological performances. In this case, the optimal solution will be used to construct mutant strains. With the physiological comparison between the parent and mutant strains, ideal anti-acid components with significant effect against acid stress and little perturbation on metabolism will be confirmed. On this basis, the universality of these anti-acid components will be studied further combined with physiological differences between different strains. Moreover，this study will lay a solid theoretical foundation to strengthen the anti-acid performance of industrial microorganisms.