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bioRxiv · 10.1101/2022.10.12.511978

Humanized CB1R and CB2R yeast biosensors enable facile screening of cannabinoid compounds

Mulvihill, C. J.·Lutgens, J.·Gollihar, J. D.·Bachanova, P.·Marcotte, E. M.·Ellington, A. D.·Gardner, E. C.
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Abstract

Yeast expression of human G Protein Coupled Receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. The Cannabinoid receptors type 1 and 2 (CB1/2R) are of particular interest, given the cornucopia of natural and synthetic cannabinoids being explored as therapeutics. We show for the first time that engineering the N-terminus of CB1R allows for efficient signal transduction in yeast, and that engineering the sterol composition of the yeast membrane optimizes CB2R performance. Using the dual cannabinoid biosensors, large libraries of synthetic cannabinoids and terpenes could be quickly screened to elucidate known and novel structure-activity relationships, including compounds and trends that more selectively target each of the two receptors. The biosensor strains offer a ready platform for evaluating the activity of new synthetic cannabinoids, monitoring drugs of abuse, and developing molecules that target the therapeutically important CB2R receptor while minimizing psychoactive effects.

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Mulvihill, C. J., Lutgens, J., Gollihar, J. D., Bachanova, P., Marcotte, E. M., Ellington, A. D., Gardner, E. C.. 2022-10-12. Humanized CB1R and CB2R yeast biosensors enable facile screening of cannabinoid compounds. https://doi.org/10.1101/2022.10.12.511978

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