Transcription Factors: A Promising Third-Generation Core Sensing Element for Developing Low-Cost, On-Site Rapid Detection Technologies for Food Contaminants

Biosensors couple biological recognition elements with signal transducers to provide rapid, low-cost alternatives to conventional food analysis. Beyond antibodies and aptamers, transcription factors (TFs) are emerging as highly sensitive recognition modules because they deliver intrinsic transcriptional signal amplification. TF-based sensors are effective for food-relevant small molecules and heavy metal ions that are often difficult to detect with antibodies, and they can be produced inexpensively in microbial systems. Enabled by synthetic biology, these platforms are advancing toward practical use in food safety monitoring. This review summarizes TF architecture, discovery, and engineering; introduces a proximal mutagenesis strategy; and outlines a coordinated approach to optimize TFs and their cognate DNA-binding sites. The review further integrates TF engineering with artificial intelligence (AI)-assisted analysis to identify and characterize performance-defining functional sites and to highlight remaining challenges and opportunities for food safety diagnostics.