Control of gene expression is crucial for several biotechnological applications, especially for implementing predictable and controllable genetic circuits. Such circuits are often implemented with a transcriptional regulator activated by a specific signal. These regulators should work independently of the host machinery, with low gratuitous induction or crosstalk with host components. Moreover, the signal should also be orthogonal, recognized only by the regulator with minimal interference with the host operation. In this context, transcriptional regulators activated by plant metabolites as flavonoids emerge as candidates to control gene expression in bacteria. However, engineering novel circuits requires the characterization of the genetic parts (e.g., genes, promoters, ribosome binding sites, and terminators) in the host of interest. Therefore, we decomposed the QdoR regulatory system of B. subtilis, responsive to the flavonoid quercetin, and reassembled its parts into genetic circuits programmed to have different levels of gene expression and noise dependent on the concentration of quercetin. We showed that only one of the promoters regulated by QdoR worked well in E. coli, enabling the construction of other circuits induced by quercetin. The QdoR expression was modulated with constitutive promoters of different transcriptional strengths, leading to low expression levels when QdoR was highly expressed and vice versa. E. coli strains expressing high and low levels of QdoR were mixed and induced with the same quercetin concentration, resulting in two stable populations expressing different levels of their gene reporters. Besides, we demonstrated that the level of QdoR repression generated different noise levels in gene expression dependent on the concentration of quercetin. The circuits presented here can be exploited in applications requiring adjustment of gene expression and noise using a highly available and natural inducer as quercetin.

基因表达的控制对于多种生物技术应用至关重要，尤其是对于实现可预测和可控的遗传回路。此类电路通常使用由特定信号激活的转录调节器来实现。这些调节器应独立于主机机器工作，与主机组件的无故感应或串扰较低。此外，信号也应该是正交的，只能由调节器识别，对主机操作的干扰最小。在这种情况下，由植物代谢物作为类黄酮激活的转录调节因子成为控制细菌基因表达的候选物。然而，工程化新电路需要对目标宿主中的遗传部分（例如，基因、启动子、核糖体结合位点和终止子）进行表征。所以，枯草芽孢杆菌，对类黄酮槲皮素有反应，并将其部分重新组装成基因回路，这些回路被编程为具有不同水平的基因表达和噪声，这取决于槲皮素的浓度。我们表明，只有一个受 QdoR 调控的启动子在大肠杆菌，能够构建由槲皮素诱导的其他电路。QdoR 表达受到不同转录强度的组成型启动子的调节，导致 QdoR 高表达时表达水平低，反之亦然。大肠杆菌将表达高水平和低水平 QdoR 的菌株混合并用相同的槲皮素浓度诱导，导致两个稳定的种群表达不同水平的基因报告基因。此外，我们证明 QdoR 抑制水平在基因表达中产生不同的噪音水平，这取决于槲皮素的浓度。此处介绍的电路可用于需要使用高度可用的天然诱导剂（如槲皮素）调整基因表达和噪声的应用。