Plug-and-Play Metabolic Transducers Expand the Chemical Detection Space of Cell-Free Biosensors

Cell-free transcription-translation systems have great potential for biosensing, yet the range of detectable chemicals is limited. Here we provide a framework to expand the range of molecules detectable by cell-free biosensors by combining synthetic metabolic cascades with transcription factor-based networks. These hybrid cell-free biosensors are highly-sensitive and have a fast response and high-dynamic range. This work provides a foundation to engineer modular cell-free biosensors tailored for many applications.