Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute, Houston, TX 77030, USA.
Int J Mol Sci. 2024 May 31;25(11):6060. doi: 10.3390/ijms25116060.
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.
酵母表达的人类 G 蛋白偶联受体（GPCR）可作为一种生物传感器平台，用于检测药物。鉴于正在探索大量的天然和合成大麻素作为治疗方法，大麻素受体 1 型（CB1R）特别引人注目。我们首次表明，对 CB1R 的 N 端进行工程改造可以在酵母中实现有效的信号转导，并且酵母膜的固醇组成的工程改造可以调节其性能。使用工程化的大麻素生物传感器，我们证明可以快速筛选大型合成大麻素和萜烯文库，以阐明已知和新的结构-活性关系。该生物传感器菌株为评估新合成大麻素的活性、监测滥用药物以及开发治疗分子提供了一个现成的平台。
