SENSOR SET-UP: To detect a small molecule of interest (the ligand), a conditionally stable ligand-binding domain (LBD) is fused to a reporter, such as green fluorescent protein (GFP). The complex degrades if the ligand is not present (1), and activates the reporter when it is (2). In another demonstration of this sensor, researchers connected the LBD to a DNA-binding domain (DBD) (3). When the ligand is present, the DBD hooks onto to a site in the genome (red), which results in the expression of a specified reporter gene (yellow) (4).© GEORGE RETSECK; ELIFE, 4:E10606, 2015
The ability to detect small molecules of interest has wide applicability in biological research, biotechnology, and especially synthetic biology. For example, turning cells into factories that produce small molecules—for use as drugs, biofuels, and more—is the goal of many synthetic biology endeavors. Just like regular factories, cellular ones require optimization. “In many cases we can create a valuable compound, but at a very low yield,” says Dan Mandell, a postdoctoral researcher in George Church’s Harvard University lab.
Scientists can attempt to improve production, but there is often no fast way to know whether they’ve succeeded. Mass spectrometry, for example, is a very sensitive and reliable way to detect small molecule production, says Mandell, but it’s “somewhat cumbersome, expensive, and slow.”
Specific sensors exist for only ...
