| Title: | Screening microbially produced Delta(9)-tetrahydrocannabinol using a yeast biosensor workflow |
| Author(s): | Shaw WM; Zhang Y; Lu X; Khalil AS; Ladds G; Luo X; Ellis T; |
| Address: | "Biological Design Center, Boston University, Boston, MA, 02215, USA. Department of Biomedical Engineering, Boston University, Boston, MA, 02215, USA. Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK. Imperial College Centre for Synthetic Biology, Imperial College London, London, SW7 2AZ, UK. Center for Synthetic Biochemistry, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA. Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, UK. Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK. t.ellis@imperial.ac.uk. Imperial College Centre for Synthetic Biology, Imperial College London, London, SW7 2AZ, UK. t.ellis@imperial.ac.uk" |
| DOI: | 10.1038/s41467-022-33207-x |
| ISSN/ISBN: | 2041-1723 (Electronic) 2041-1723 (Linking) |
| Abstract: | "Microbial production of cannabinoids promises to provide a consistent, cheaper, and more sustainable supply of these important therapeutic molecules. However, scaling production to compete with traditional plant-based sources is challenging. Our ability to make strain variants greatly exceeds our capacity to screen and identify high producers, creating a bottleneck in metabolic engineering efforts. Here, we present a yeast-based biosensor for detecting microbially produced Delta(9)-tetrahydrocannabinol (THC) to increase throughput and lower the cost of screening. We port five human cannabinoid G protein-coupled receptors (GPCRs) into yeast, showing the cannabinoid type 2 receptor, CB2R, can couple to the yeast pheromone response pathway and report on the concentration of a variety of cannabinoids over a wide dynamic and operational range. We demonstrate that our cannabinoid biosensor can detect THC from microbial cell culture and use this as a tool for measuring relative production yields from a library of Delta(9)-tetrahydrocannabinol acid synthase (THCAS) mutants" |
| Keywords: | *Biosensing Techniques *Cannabinoids/metabolism Dronabinol/metabolism Humans Pheromones/metabolism Saccharomyces cerevisiae/genetics/metabolism Workflow; |
| Notes: | "MedlineShaw, William M Zhang, Yunfeng Lu, Xinyu Khalil, Ahmad S Ladds, Graham Luo, Xiaozhou Ellis, Tom eng BB/M503381/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom BB/R002614/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2022/09/21 Nat Commun. 2022 Sep 20; 13(1):5509. doi: 10.1038/s41467-022-33207-x" |
