Gene duplication and mutation has led to the formation of many different two-component systems (TSC), allowing for a diverse range of extracellular ligands to be detected. By accumulating mutations in the new, duplicated TCS genes, genetic drift leads to the separation of the two pathways and ultimately to the formation of a new pathway.
Synthetic biology techniques could exploit TCS, allowing biochemical logic to be introduced into cells. This would allow specific extracellular stimuli to control gene expression. A potential use for this sort of logic could be detecting specific molecules to express a reporter (such as GFP). Using de novo protein design, novel histidine kinases (HK) could detect desired molecules, such as explosives, drugs, or pathogens. Using a response regulator (RR) targeting the reporter gene, it could be easy to observe the presence of a specific compound.
Tying cell fitness to the activation of the HK, in the presence of the target molecule, and using a directed evolution approach, could be an alternative to de novo protein design.
Although it would be easier to use a simple chemical assay, it may not be possible to develop accurate assays for all molecules. Using bacterial assays could be an alternative to this.