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

Karel Miettinen, Nattawat Leelahakorn, Aldo Almeida, Yong Zhao, Lukas R. Hansen, Iben E. Nikolajsen, Jens B. Andersen, Michael Givskov, Dan Staerk, Søren Bak and Sotirios C. Kampranis ()
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Karel Miettinen: University of Copenhagen
Nattawat Leelahakorn: University of Copenhagen
Aldo Almeida: University of Copenhagen
Yong Zhao: University of Copenhagen
Lukas R. Hansen: University of Copenhagen
Iben E. Nikolajsen: University of Copenhagen
Jens B. Andersen: University of Copenhagen
Michael Givskov: University of Copenhagen
Dan Staerk: University of Copenhagen
Søren Bak: University of Copenhagen
Sotirios C. Kampranis: University of Copenhagen

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31357-6

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