Abstract
G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors in humans. Over 800 GPCRs regulate the (patho)biology of every organ, tissue, and cell type. Consequently, GPCRs are the most prominent therapeutic targets in medicine. Although over 30% of current U.S. Food and Drug Administration-approved drugs target GPCR signaling, most receptors remain understudied and therapeutically underutilized. Challenges include an incomplete understanding of GPCR signaling, pharmacology, structural biology, and the multiplicity of endogenous GPCR ligands, in addition to a scarcity of biological and pharmacological tools for elucidating GPCR-mediated cellular processes beyond initial signaling events. Various mammalian, insect, and yeast cell models currently address some of these needs. Here, we review recent advances in yeast synthetic biology that are helping to catalyze new and unexpected conceptual and technical breakthroughs in GPCR-based medicine and biotechnology.
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