Transcription factor-based biosensors: a molecular-guided approach for natural product engineering.

Natural products and their derivatives offer a rich source of chemical and biological diversity; however, traditional engineering of their biosynthetic pathways to improve yields and access to unnatural derivatives requires a precise understanding of their enzymatic processes. High-throughput screening platforms based on allosteric transcription-factor based biosensors can be leveraged to overcome the screening bottleneck to enable searching through large libraries of pathway/strain variants. Herein, the development and application of engineered allosteric transcription factor-based biosensors is described that enable optimization of precursor availability, product titers, and downstream product tailoring for advancing the natural product bioeconomy.