| Summary: | Abstract Background Whole cell biosensors provide a simple method for the detection of heavy metals. However, previous designs of them rely primarily on simulation of heavy metal resistance systems of bacteria. Results This study proposes a strategy for the rational design of metal detection circuits based on sensor proteins of the MerR family. Our results indicate the expression level of sensor protein can be used as a “rheostat” for tuning detection sensitivity with parabola curves to represent the relationships between the detection slopes and the sensor protein levels. This circuits design strategy (named as “Parabola Principle”), is used as a guide for the discovery of optimum metal detection circuits, and the design of biosensors with specific metal detection characteristics. For example, visible qualitative Hg (II) biosensors with a threshold of 0.05 mg/L are successfully constructed. Conclusions These results indicate the feasibility of developing a sensor that is much more tunable than what is presented. Graphical abstract
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