Custom-made transcriptional biosensors for metabolic engineering

[Display omitted] •Successful examples of transcriptional biosensor implementations are presented.•Various engineering strategies extend the space of detectable chemicals.•Novel strategies exist to transform metabolite-responding proteins into biosensors.•Mathematical models of varying complexity can help tune biosensor properties.•Biosensors using or designed for cell-free systems are presented. Transcriptional biosensors allow screening, selection, or dynamic regulation of metabolic pathways, and are, therefore, an enabling technology for faster prototyping of metabolic engineering and sustainable chemistry. Recent advances have been made, allowing for routine use of heterologous transcription factors, and new strategies such as chimeric protein design allow engineers to tap into the reservoir of metabolite-binding proteins. However, extending the sensing scope of biosensors is only the first step, and computational models can help in fine-tuning properties of biosensors for custom-made behavior. Moreover, metabolic engineering is bound to benefit from advances in cell-free expression systems, either for faster prototyping of biosensors or for whole-pathway optimization, making it both a means and an end in biosensor design.