Expanding Biosensing Abilities through Computer-Aided Design of Metabolic Pathways

Detection of chemical signals is critical for cells in
nature as well as in synthetic biology, where they serve as inputs
for designer circuits. Important progress has been made in the
design of signal processing circuits triggering complex biological
behaviors, but the range of small molecules recognized by
sensors as inputs is limited. The ability to detect new molecules
will increase the number of synthetic biology applications, but
direct engineering of tailor-made sensors takes time. Here we
describe a way to immediately expand the range of biologically
detectable molecules by systematically designing metabolic pathways that transform nondetectable molecules into molecules for
which sensors already exist. We leveraged computer-aided design to predict such sensing-enabling metabolic pathways, and we
built several new whole-cell biosensors for molecules such as cocaine, parathion, hippuric acid, and nitroglycerin