TY - JOUR
T1 - A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination
AU - Miettinen, Karel
AU - Leelahakorn, Nattawat
AU - Almeida Robles, Aldo Ricardo
AU - Zhao, Yong
AU - Hansen, Lukas Ronild
AU - Nikolajsen, Iben Egebæk
AU - Andersen, Jens Bo
AU - Givskov, Michael
AU - Stærk, Dan
AU - Bak, Søren
AU - Kampranis, Sotirios
PY - 2022
Y1 - 2022
N2 - The decriminalization of cannabis and the growing interest in cannabinoids as therapeutics require efficient methods to discover novel compounds and monitor cannabinoid levels in human samples and products. However, current methods are limited by the structural diversity of the active compounds. Here, we construct a G-protein coupled receptor-based yeast whole-cell biosensor, optimize it to achieve high sensitivity and dynamic range, and prove its effectiveness in three real-life applications. First, we screen a library of compounds to discover two novel agonists and four antagonists and demonstrate that our biosensor can democratize GPCR drug discovery by enabling low-cost high-throughput analysis using open-source automation. Subsequently, we bioprospect 54 plants to discover a novel phytocannabinoid, dugesialactone. Finally, we develop a robust portable device, analyze body-fluid samples, and confidently detect illicit synthetic drugs like “Spice”/“K2”. Taking advantage of the extensive sensing repertoire of GPCRs, this technology can be extended to detect numerous other compounds.
AB - The decriminalization of cannabis and the growing interest in cannabinoids as therapeutics require efficient methods to discover novel compounds and monitor cannabinoid levels in human samples and products. However, current methods are limited by the structural diversity of the active compounds. Here, we construct a G-protein coupled receptor-based yeast whole-cell biosensor, optimize it to achieve high sensitivity and dynamic range, and prove its effectiveness in three real-life applications. First, we screen a library of compounds to discover two novel agonists and four antagonists and demonstrate that our biosensor can democratize GPCR drug discovery by enabling low-cost high-throughput analysis using open-source automation. Subsequently, we bioprospect 54 plants to discover a novel phytocannabinoid, dugesialactone. Finally, we develop a robust portable device, analyze body-fluid samples, and confidently detect illicit synthetic drugs like “Spice”/“K2”. Taking advantage of the extensive sensing repertoire of GPCRs, this technology can be extended to detect numerous other compounds.
U2 - 10.1038/s41467-022-31357-6
DO - 10.1038/s41467-022-31357-6
M3 - Journal article
C2 - 35760809
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 3664
ER -