Bacterial two-component systems as sensors for synthetic biology applications

Two-component systems (TCSs) are a ubiquitous family of signal transduction pathways that enable bacteria to sense and respond to physical, chemical, and biological stimuli outside and inside the cell. Synthetic biologists have begun to repurpose TCSs for applications in optogenetics, materials science, gut microbiome engineering, and soil nutrient bio-sensing, among others. New engineering methods including genetic refactoring, DNA-binding domain swapping, detection threshold tuning, and phosphorylation cross-talk insulation are being used to increase the reliability of TCS sensor perfor-mance and tailor TCS signaling properties to the requirements of specific applications. There is now potential to combine these methods with large-scale gene synthesis and laboratory screening to discover the inputs sensed by many uncharac-terized TCSs and develop a large new family of genetically -encoded sensors that respond to an unrivaled breadth of stimuli.

Automated summary

Two-component systems (TCSs) are a common family of signal transduction pathways used by bacteria to sense and respond to various stimuli. Synthetic biologists are repurposing TCSs for applications in different fields, with the potential to discover new inputs and develop a wide range of genetically-encoded sensors that respond to diverse stimuli.