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Microbial populations are a promising model for achieving microbial cooperation to produce valuable chemicals. However, regulating the phenotypic structure of microbial populations remains challenging. In this study, a programmed lysis system (PLS) is developed to reprogram microbial cooperation to enhance chemical production. First, a colicin M -based lysis unit is constructed to lyse <i>Escherichia coli</i>. Next, a programmed switch, based on proteases, is designed to regulate the effective lysis unit time. Finally, a PLS is constructed for chemical production by combining the lysis unit with a programmed switch. As a result, poly (lactate-<i>co</i>-3-hydroxybutyrate) production is switched from PLH synthesis to PLH release, and the content of free PLH is increased 283%. Furthermore, butyrate production with <i>E. coli</i> consortia is switched from <i>E. coli </i>BUT003 to <i>E. coli</i> BUT004, thereby increasing butyrate production to 41.61 g/L. These results indicate the applicability of engineered microbial populations for improving the metabolic division of labor to increase the efficiency of microbial cell factories.

微生物种群是实现微生物协同作用以生产高价值化学品的极具前景的研究模型。然而，调控微生物种群的表型结构仍颇具挑战。本研究开发了一种程序化裂解系统（programmed lysis system, PLS），通过重编程微生物协同模式以强化化学品合成能力。首先，构建了基于大肠杆菌素M（colicin M）的裂解单元以裂解大肠杆菌（Escherichia coli）；其次，设计了基于蛋白酶（protease）的程序化调控开关，精准调控裂解单元的有效作用时序；最后，将该裂解单元与程序化调控开关相结合，构建了用于化学品生产的PLS。实验结果表明，聚（乳酸-共聚-3-羟基丁酸酯）（poly(lactate-co-3-hydroxybutyrate), PLH）的生产模式从PLH合成阶段切换至PLH释放阶段，游离PLH的含量提升283%。此外，以大肠杆菌（Escherichia coli, E. coli）复合菌群进行的丁酸生产，其生产菌株从大肠杆菌BUT003切换为大肠杆菌BUT004，最终丁酸产量提升至41.61 g/L。上述结果证实，工程化改造的微生物种群可通过优化代谢分工，提升微生物细胞工厂的生产效率，具备良好的应用潜力。