Abstract: Designer microbes that convert sugars into bioproducts provide a sustainable alternative to the synthesis of chemicals from petroleum. One of the major challenges in the engineering of microbes for the production of chemicals is the rapid identification of the highest chemical-producing microbe from a pool, akin to finding a needle in a haystack. Chromatography-based methods for the strain-screening step limit the screening throughput to ~100 chemical-producing microbes per day. Biosensors that link chemical detection to fluorescence have the potential to enable the screening of more than a million chemical-producing microbes per day. Here, I will present work on the rapid engineering of GPCR-based sensors to detect different chemicals from advanced biofuels and pharmaceutical-like compounds. We are now using these sensors for the high-throughput screening of chemical producing microbes, and considering how this throughput now allow us to apply evolutionary approaches to the bioproduction of biofuels and other non-colorimetric chemicals.