Transcription-factor-based biosensors (TFBs) are often used for metabolite detection, adaptive evolution, and metabolic flux control. However, designing TFBs with superior performance for applications in synthetic biology remains challenging. Specifically, natural TFBs often do not meet real-time detection requirements owing to their slow response times and inappropriate dynamic ranges, detection ranges, sensitivity, and selectivity. Furthermore, designing and optimizing complex dynamic regulation networks is time-consuming and labor-intensive. This Review highlights TFB-based applications and recent engineering strategies ranging from traditional trial-and-error approaches to novel computer-model-based rational design approaches. The limitations of the applications and these engineering strategies are additionally reviewed.
Keywords: adaptive evolution; dose−response; dynamic regulation; genetic circuits; high-throughput screening.