Transcription factor-based biosensor: A molecular-guided approach for advanced biofuel synthesis

As a sustainable and renewable alternative to petroleum fuels, advanced biofuels shoulder the responsibility of energy saving, emission reduction and environmental protection. Traditional engineering of cell factories for production of advanced biofuels lacks efficient high-throughput screening tools and regulating systems, impeding the improvement of cellular productivity and yield. Transcription factor-based biosensors have been widely applied to monitor and regulate microbial cell factory products due to the advantages of fast detection and in-situ screening. This review updates the design and application of transcription factor-based biosensors tailored for advanced biofuels and related intermediates. The construction and genetic parts selection principle of biosensors are discussed. Strategies to enhance the performance of biosensor, including regulating promoter strength and RBS strength, optimizing plasmid copy number, implementing genetic amplifier, and modulating the structure of transcription factor, have also been summarized. We further review the application of biosensors in high-throughput screening of new metabolic engineering targets, evolution engineering, confirmation of protein function, and dynamic regulation of metabolic flux for higher production of advanced biofuels. At last, we discuss the current limitations and future trends of transcription factor-based biosensors.