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Two-Component Biosensors: Unveiling the Mechanisms of Predictable Tunability.
ACS Synthetic Biology ( IF 4.7 ) Pub Date : 2020-05-05 , DOI: 10.1021/acssynbio.0c00010
Eva Gonzalez-Flo 1 , Maria Elisenda Alaball 1, 2 , Javier Macia 1
Affiliation  

Many studies have been devoted to the engineering of cellular biosensors by exploiting intrinsic natural sensors. However, biosensors rely not only on input detection but also on an adequate response range. It is therefore often necessary to tune natural systems to meet the demands of specific applications in a predictable manner. In this study, we explored the customizability of two-component bacterial biosensors by modulating the main biosensor component, i.e., the receptor protein. We developed a mathematical model that describes the functional relationship between receptor abundance and activation threshold, sensitivity, dynamic range, and operating range. The defined mathematical framework allows the design of the genetic architecture of a two-component biosensor that can perform as required with minimal genetic engineering. To experimentally validate the model and its predictions, a library of biosensors was constructed. The good agreement between theoretical designs and experimental results indicates that modulation of receptor protein abundance allows optimization of biosensor designs with minimal genetic engineering.

中文翻译:

两组分生物传感器:揭示可预测的可调性机制。

通过利用固有的自然传感器,许多研究致力于细胞生物传感器的工程设计。但是,生物传感器不仅依赖于输入检测,而且还依赖于适当的响应范围。因此,通常需要以可预测的方式调整自然系统以满足特定应用程序的需求。在这项研究中,我们通过调节生物传感器的主要成分,两组分细菌生物传感器的可定制性,受体蛋白。我们开发了一个数学模型来描述受体丰度与激活阈值,灵敏度,动态范围和工作范围之间的功能关系。定义的数学框架允许设计一种两组分生物传感器的遗传结构,该遗传传感器可以在需要最少基因工程的情况下按要求执行。为了通过实验验证模型及其预测,构建了生物传感器库。理论设计和实验结果之间的良好一致性表明,受体蛋白丰度的调节允许以最少的基因工程优化生物传感器设计。
更新日期:2020-06-19
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