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A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination.


ABSTRACT: 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.

SUBMITTER: Miettinen K 

PROVIDER: S-EPMC9237071 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination.

Miettinen Karel K   Leelahakorn Nattawat N   Almeida Aldo A   Zhao Yong Y   Hansen Lukas R LR   Nikolajsen Iben E IE   Andersen Jens B JB   Givskov Michael M   Staerk Dan D   Bak Søren S   Kampranis Sotirios C SC  

Nature communications 20220627 1


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 CB<sub>2</sub> receptor-based biosensor, optimize it to achieve high sensitivity and dynamic range, an  ...[more]

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