A Humanized CB1R Yeast Biosensor Enables Facile Screening of Cannabinoid Compounds-Reference-Cited by-同舟云学术

A Humanized CB1R Yeast Biosensor Enables Facile Screening of Cannabinoid Compounds

Published:2024-05-31 Issue:11 Volume:25 Page:6060
ISSN:1422-0067
Container-title:International Journal of Molecular Sciences
language:en
Short-container-title:IJMS

Author:

Mulvihill Colleen J.¹,Lutgens Joshua D.¹^ORCID,Gollihar Jimmy D.²^ORCID,Bachanová Petra¹,Tramont Caitlin¹,Marcotte Edward M.¹^ORCID,Ellington Andrew D.¹,Gardner Elizabeth C.¹³

Affiliation:

1. Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA

2. Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute, Houston, TX 77030, USA

3. Department of Bioengineering, Rice University, 6100 Main St., Houston, TX 77005, USA

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.

Funder

cooperative agreement between the University of Texas at Austin and DEVCOM Army Research Laboratory

Welch Foundation

Army Research Office

NIH

National Institute of Health

Publisher

MDPI AG

Link

https://www.mdpi.com/1422-0067/25/11/6060/pdf

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