A Humanized CB1R Yeast Biosensor Enables Facile Screening of Cannabinoid Compounds

Colleen J. Mulvihill; Joshua D. Lutgens; Jimmy D. Gollihar; Petra Bachanová; Caitlin Tramont; Edward M. Marcotte; Andrew D. Ellington; Elizabeth C. Gardner

doi:10.3390/ijms25116060

A Humanized CB1R Yeast Biosensor Enables Facile Screening of Cannabinoid Compounds

Colleen J. Mulvihill, Joshua D. Lutgens, Jimmy D. Gollihar, Petra Bachanová, Caitlin Tramont, Edward M. Marcotte, Andrew D. Ellington, Elizabeth C. Gardner

Research output: Contribution to journal › Article › peer-review

Abstract

Yeast expression of human G-protein-coupled receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. Cannabinoid receptor type 1 (CB1R) is 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 modulates its performance. Using an engineered cannabinoid biosensor, we demonstrate that large libraries of synthetic cannabinoids and terpenes can be quickly screened to elucidate known and novel structure–activity relationships. The biosensor strains offer a ready platform for evaluating the activity of new synthetic cannabinoids, monitoring drugs of abuse, and developing therapeutic molecules.

Original language	English (US)
Article number	6060
Journal	International journal of molecular sciences
Volume	25
Issue number	11
DOIs	https://doi.org/10.3390/ijms25116060
State	Published - May 31 2024

Keywords

G-protein-coupled receptors
cannabinoid receptors
humanized yeast
Receptor, Cannabinoid, CB1/metabolism
Saccharomyces cerevisiae/metabolism
Cannabinoids/chemistry
Biosensing Techniques/methods
Humans
Structure-Activity Relationship
Signal Transduction/drug effects

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.3390/ijms25116060

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title = "A Humanized CB1R Yeast Biosensor Enables Facile Screening of Cannabinoid Compounds",

abstract = "Yeast expression of human G-protein-coupled receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. Cannabinoid receptor type 1 (CB1R) is 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 modulates its performance. Using an engineered cannabinoid biosensor, we demonstrate that large libraries of synthetic cannabinoids and terpenes can be quickly screened to elucidate known and novel structure–activity relationships. The biosensor strains offer a ready platform for evaluating the activity of new synthetic cannabinoids, monitoring drugs of abuse, and developing therapeutic molecules.",

keywords = "G-protein-coupled receptors, cannabinoid receptors, humanized yeast, Receptor, Cannabinoid, CB1/metabolism, Saccharomyces cerevisiae/metabolism, Cannabinoids/chemistry, Biosensing Techniques/methods, Humans, Structure-Activity Relationship, Signal Transduction/drug effects",

author = "Mulvihill, {Colleen J.} and Lutgens, {Joshua D.} and Gollihar, {Jimmy D.} and Petra Bachanov{\'a} and Caitlin Tramont and Marcotte, {Edward M.} and Ellington, {Andrew D.} and Gardner, {Elizabeth C.}",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

year = "2024",

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day = "31",

doi = "10.3390/ijms25116060",

language = "English (US)",

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AU - Mulvihill, Colleen J.

AU - Lutgens, Joshua D.

AU - Gollihar, Jimmy D.

AU - Bachanová, Petra

AU - Tramont, Caitlin

AU - Marcotte, Edward M.

AU - Ellington, Andrew D.

AU - Gardner, Elizabeth C.

PY - 2024/5/31

Y1 - 2024/5/31

N2 - Yeast expression of human G-protein-coupled receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. Cannabinoid receptor type 1 (CB1R) is 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 modulates its performance. Using an engineered cannabinoid biosensor, we demonstrate that large libraries of synthetic cannabinoids and terpenes can be quickly screened to elucidate known and novel structure–activity relationships. The biosensor strains offer a ready platform for evaluating the activity of new synthetic cannabinoids, monitoring drugs of abuse, and developing therapeutic molecules.

AB - Yeast expression of human G-protein-coupled receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. Cannabinoid receptor type 1 (CB1R) is 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 modulates its performance. Using an engineered cannabinoid biosensor, we demonstrate that large libraries of synthetic cannabinoids and terpenes can be quickly screened to elucidate known and novel structure–activity relationships. The biosensor strains offer a ready platform for evaluating the activity of new synthetic cannabinoids, monitoring drugs of abuse, and developing therapeutic molecules.

KW - G-protein-coupled receptors

KW - cannabinoid receptors

KW - humanized yeast

KW - Receptor, Cannabinoid, CB1/metabolism

KW - Saccharomyces cerevisiae/metabolism

KW - Cannabinoids/chemistry

KW - Biosensing Techniques/methods

KW - Humans

KW - Structure-Activity Relationship

KW - Signal Transduction/drug effects

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A Humanized CB1R Yeast Biosensor Enables Facile Screening of Cannabinoid Compounds

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ASJC Scopus subject areas

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