Bacteria can be harnessed to synthesise high-value chemicals. A promising strategy for increasing productivity uses inducible control systems to switch metabolism from growth to chemical synthesis once a large population of cell factories are generated. However, use of expensive chemical inducers limits scalability of this approach for biotechnological applications. Switching using cheap nutrients is an appealing alternative, but their tightly regulated uptake and consumption again limits scalability. Here, using mathematical models of fatty acid uptake in E. coli as an exemplary case study, we unravel how the cell's native regulation and program of induction can be engineered to minimise inducer usage. We show that integrating positive feedback loops into the circuitry creates an irreversible metabolic switch, which, requiring only temporary induction, drastically reduces inducer usage. Our proposed switch should be widely applicable, irrespective of the product of interest, and brings closer the realisation of scalable and sustainable microbial chemical production.

中文翻译：

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设计不可逆的代谢开关，可扩展地诱导微生物化学生产

细菌可用于合成高价值的化学品。一旦产生大量细胞工厂，增加生产力的一种有前途的策略就是使用诱导型控制系统将新陈代谢从生长转换为化学合成。但是，昂贵的化学诱导剂的使用限制了该方法在生物技术应用中的可扩展性。换用廉价的营养素是一种吸引人的选择，但严格控制它们的摄取和消耗又限制了其可扩展性。在这里，使用大肠杆菌中脂肪酸摄取的数学模型作为一个示例性案例研究，我们将揭示如何设计细胞的天然调控和诱导程序以最大程度地减少诱导剂的使用。我们表明，将正反馈回路集成到电路中会产生不可逆的新陈代谢开关，仅需要临时感应就可以大大减少感应器的使用。我们建议的开关应广泛适用，而与所关注的产品无关，并且可以更紧密地实现可扩展且可持续的微生物化学品生产。