Engineered bacteria promise to revolutionize diagnostics and therapeutics, yet many applications are precluded by the limited number of detectable signals. Here we present a general framework to engineer synthetic receptors enabling bacterial cells to respond to novel ligands. These receptors are activated via ligand-induced dimerization of a single-domain antibody fused to monomeric DNA-binding domains (split-DBDs). Using E. coli as a model system, we engineer both transmembrane and cytosolic receptors using a VHH for ligand detection and demonstrate the scalability of our platform by using the DBDs of two different transcriptional regulators. We provide a method to optimize receptor behavior by finely tuning protein expression levels and optimizing interdomain linker regions. Finally, we show that these receptors can be connected to downstream synthetic gene circuits for further signal processing. The general nature of the split-DBD principle and the versatility of antibody-based detection should support the deployment of these receptors into various hosts to detect ligands for which no receptor is found in nature.

中文翻译：

---

一个模块化的受体平台，可扩展细菌的感测范围。

工程细菌有望彻底改变诊断和治疗方法，但由于可检测信号的数量有限，许多应用都被排除在外。在这里，我们提出了一个总体框架来工程化合成受体，使细菌细胞能够对新型配体作出反应。这些受体通过配体诱导的与单体DNA结合结构域（split-DBDs）融合的单结构域抗体的二聚化而被激活。使用大肠杆菌作为模型系统，我们使用VHH对跨膜受体和胞质受体进行工程设计，以进行配体检测，并通过使用两种不同转录调节剂的DBD来证明我们平台的可扩展性。我们提供了一种通过微调蛋白质表达水平和优化域间接头区域来优化受体行为的方法。最后，我们表明，这些受体可以连接到下游的合成基因电路，以进行进一步的信号处理。分裂DBD原理的一般性质和基于抗体的检测的多功能性应支持将这些受体部署到各种宿主中，以检测在自然界中找不到受体的配体。