TetR-based biosensors for tetracycline detection: A review of allosteric mechanism, applications, and engineering

The presence of tetracycline (TC) residues in food and environmental matrices poses persistent risks to food safety and public health, highlighting the need for efficient detection strategies. The tetracycline repressor protein (TetR), a bacterial allosteric transcription factor (aTF), has emerged as a promising molecular recognition element for biosensor development. This review summarizes recent advances in TetR-based biosensors for TC detection. We first outline the structural features and molecular recognition mechanisms of TetR, highlighting the properties that make it suitable for biosensing applications. We then systematically summarize various TetR-based biosensing platforms and analyze the functional roles of TetR within these systems. Furthermore, we review recent progress in protein engineering aimed at optimizing TetR affinity, specificity, and regulatory logic. Finally, current challenges and prospects for practical applications are discussed. This work clarifies the pivotal role of TetR in TC biosensors and provides a reference framework for the application of other aTFs in biosensor design.