Natural microbial populations exploit phenotypic heterogeneity for survival and adaptation. However, in engineering biology, limiting the sources of variability is a major focus. Here we show that intentionally coupling distinct plasmids via shared replication mechanisms enables bacterial populations to adapt to their environment. We demonstrate that plasmid coupling of carbon-metabolizing operons facilitates copy number tuning of an essential but burdensome construct through the action of a stably maintained, non-essential plasmid. For specific cost–benefit situations, incompatible two-plasmid systems can stably persist longer than compatible ones. We also show using microfluidics that plasmid coupling of synthetic constructs generates population-state memory of previous environmental adaptation without additional regulatory control. This work should help to improve the design of synthetic populations by enabling adaptive engineered strains to function under changing growth conditions without strict fine-tuning of the genetic circuitry.

自然微生物种群利用表型异质性来生存和适应。然而，在工程生物学中，限制变异的来源是一个主要焦点。在这里，我们表明，通过共享复制机制有意耦合不同的质粒使细菌群体能够适应其环境。我们证明，碳代谢操纵子的质粒偶联通过稳定维持的非必需质粒的作用，促进了必需但繁重的构建体的拷贝数调整。对于特定的成本效益情况，不兼容的双质粒系统可以比兼容的系统稳定地持续更长时间。我们还使用微流体技术证明，合成结构的质粒偶联会产生先前环境适应的群体状态记忆，而无需额外的监管控制。这项工作应该有助于改进合成群体的设计，使适应性工程菌株能够在不断变化的生长条件下发挥作用，而无需对遗传电路进行严格的微调。