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Abstract Two-component regulatory systems (TCRSs) mediate cellular response by coupling sensing and regulatory mechanisms. TCRSs are comprised of a histidine kinase (HK), which serves as a sensor, and a response regulator, which regulates expression of the effector gene after being phosphorylated by HK. Using these attributes, bacterial TCRSs can be engineered to design microbial systems for different applications. This review focuses on the current advances in TCRS-based biosensors and on the design of microbial systems for bioremediation and their potential application in biorefinery.