Eukaryotic cells use G-protein coupled receptors to sense diverse signals, ranging from chemical compounds to light. Here, we exploit the remarkable sensing capacity of G-protein coupled receptors to construct yeast-based biosensors for real-life applications. To establish proof-of-concept, we focus on cannabinoids because of their neuromodulatory and immunomodulatory activities. We construct a CB₂ receptor-based biosensor, optimize it to achieve high sensitivity and dynamic range, and prove its effectiveness in three applications of increasing difficulty. First, we screen a compound library to discover agonists and antagonists. Second, we analyze 54 plants to discover a new phytocannabinoid, dugesialactone. Finally, we develop a robust portable device, analyze body-fluid samples, and confidently detect designer drugs like JWH-018. These examples demonstrate the potential of yeast-based biosensors to enable diverse applications that can be implemented by non-specialists. Taking advantage of the extensive sensing repertoire of G-protein coupled receptors, this technology can be extended to detect numerous compounds.

• PMID: 35760809
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Journal Article | Research Support, Non-U.S. Gov't

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Miettinen K, Leelahakorn N, Almeida A, Zhao Y, Hansen LR, Nikolajsen IE, Andersen JB, Givskov M, Staerk D, Bak S, ... Show all

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