Olfactory Receptors as an Emerging Chemical Sensing Scaffold

Chemical biosensors are an increasingly ubiquitous part of our lives. Beyond enzyme-coupled assays, recent synthetic biology advances now allow us to hijack more complex biosensing systems to respond to difficult to detect analytes, such as chemical small molecules. Here, we briefly overview recent advances in the biosensing of small molecules, including nucleic acid aptamers, allosteric transcription factors, and two-component systems. We then look more closely at a recently developed chemical sensing system, G protein-coupled receptor (GPCR)-based sensors. Finally, we consider the chemical sensing capabilities of the largest GPCR subfamily, olfactory receptors (ORs). We examine ORs' role in nature, their potential as a biomedical target, and their ability to detect compounds not amenable for detection using other biological scaffolds. We conclude by evaluating the current challenges, opportunities, and future applications of GPCR- and OR-based sensors.