We present automated continuous evolution (ACE), a platform for the hands-free directed evolution of biomolecules. ACE pairs OrthoRep, a genetic system for continuous targeted mutagenesis of user-selected genes in vivo, with eVOLVER, a scalable and automated continuous culture device for precise, multiparameter regulation of growth conditions. By implementing real-time feedback-controlled tuning of selection stringency with eVOLVER, genes of interest encoded on OrthoRep autonomously traversed multimutation adaptive pathways to reach desired functions, including drug resistance and improved enzyme activity. The durability, scalability, and speed of biomolecular evolution with ACE should be broadly applicable to protein engineering as well as prospective studies on how selection parameters and schedules shape adaptation.

中文翻译：

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体内蛋白质的自动连续进化。

我们提出了自动连续进化（ACE），这是一个用于生物分子免提定向进化的平台。ACE 将 OrthoRep（一种用于在体内对用户选择的基因进行连续定向诱变的遗传系统）与 eVOLVER（一种可扩展的自动化连续培养装置，用于对生长条件进行精确的多参数调节）进行配对。通过使用 eVOLVER 对选择严格性进行实时反馈控制的调整，OrthoRep 上编码的感兴趣的基因可以自主地遍历多突变适应性途径，以达到所需的功能，包括耐药性和提高的酶活性。ACE 的生物分子进化的耐久性、可扩展性和速度应该广泛适用于蛋白质工程以及关于选择参数和时间表如何形状适应的前瞻性研究。