Engineering G protein-coupled receptor signalling in yeast for biotechnological and medical purposes

G protein-coupled receptors (GPCRs) comprise the largest class of membrane proteins in the human genome, with a common denominator of 7-transmembrane domains largely conserved among eukaryotes. Yeast is naturally armoured with three different GPCRs for pheromone and sugar sensing, with the pheromone pathway being extensively hijacked for characterizing heterologous GPCR signalling in a model eukaryote.

This review focuses on functional GPCR studies performed in yeast, and the elucidated hotspots for engineering and discusses both endogenous and heterologous GPCR signalling. Key emphasis will be devoted to studies describing important engineering parameters to consider for successful expression of functional coupling of GPCRs to the yeast mating pathway.

We also review the various means of applying yeast for studying GPCRs, including the use of yeast armed with heterologous GPCRs as a platform for i) deorphanisation of orphan receptors, ii) metabolic engineering of yeast for production of bioactive products, and iii) medical applications related to pathogen detection and drug discovery.

Finally, this review summarizes the current challenges related to expression of functional membrane bound GPCRs in yeast and discuss how opportunities to continue capitalising on yeast as a model chassis for functional GPCR signalling studies.