Design and engineering of genetically encoded protein biosensors for small molecules

Genetically encoded protein biosensors controlled by small organic molecules are valuable tools for many biotechnology applications, including control of cellular decisions in living cells. Here, we review recent advances in protein biosensor design and engineering for binding to novel ligands. We categorize sensor architecture as either integrated or portable, where portable biosensors uncouple molecular recognition from signal transduction. Proposed advances to improve portable biosensor development include standardizing a limited set of protein scaffolds, and automating ligand-compatibility screening and ligand-protein-interface design.