From modular engineering to practical applications: Advances in GPCR-based yeast biosensors

G protein-coupled receptors (GPCRs) are pivotal biosensing elements for biosensors due to their high ligand sensitivity and specificity. Capitalizing on these attributes, GPCR-based yeast biosensors have emerged as a powerful platform that combines conserved eukaryotic GPCR signaling with the superior genetic tractability of yeast. This synergy has accelerated the development of biosensors for diverse ligands and spurred continuous efforts to optimize their performance. This review systematically dissects engineering efforts of GPCR-based yeast biosensors through a modular framework. We summarize engineering strategies applied to the core modules-sensing (GPCRs), transduction (yeast signaling network), and output (reporters)-and highlight how these modifications enhance key performance metrics. Furthermore, we demonstrate how these engineered systems have expanded into a wide range of practical applications. Finally, we outline future directions, emphasizing the integration of artificial intelligence (AI) and synthetic biology to enable predictive and programmable design of next-generation biosensors.