Grazon, C. et al. Nat. Commun. 11, 1276 (2020).
Förster resonance energy transfer (FRET)-based biosensors are widely used in biomedical research. One challenge that is often associated with making FRET-based sensors is identifying proteins that are suitable for sensing molecules at relevant concentrations. Grazon et al. have developed a strategy to identify bacterial allosteric transcription factors that recognize a target analyte for subsequent development into biosensors. The researchers were interested in developing a progesterone sensor. For this, they turned to Pimelobacter simplex, which is known to use steroids as an energy source. They treated the bacteria with various steroids to identify upregulated gene clusters. Within the gene cluster, they identified three uncharacterized putative transcription factors and went on to validate one, a protein called SRTF1, by showing that it binds progesterone. They then used SRTF1 to develop a highly sensitive quantum-dot-based FRET reporter of progesterone.