A Modular Yeast Based GPCR Biosensor Platform for Compound Identification and Metabolic Engineering

G-protein coupled receptors (GPCRs) constitute the largest family of extracellular sensing entities in eukaryotes. The core GPCR mechanism is conserved across eukaryotes including the pheromone sensing pathway of baker’s yeast, Saccharomyces cerevisiae. We have developed a flexible modular biosensor platform by hijacking the yeast pheromone sensing pathway that in principle enables plugging in any GPCR. By optimizing a CB2 based cannabinoid biosensor we have achieved a sensitive system for cannabinoid detection with characteristics similar to those mammalian systems. As a proof-of-concept we used this biosensor to screen 71 Mexican medicinal plants for the presence of cannabinoids. Further fractionation of the plant extract and screening of the fractions enabled us to pinpoint the active compound(s) in the extract. Further expansion of this platform will be used enable the efficient optimization of cannabinoid producing cell factories.