Screening microbially produced Δ9-tetrahydrocannabinol using a yeast biosensor workflow
File(s)
Published version
Author(s)
Shaw, William
Lu, xinyu
Ellis, Thomas
Type
Journal Article
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 Δ9-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 Δ9-tetrahydrocannabinol acid synthase (THCAS) mutants.
Date Issued
2022-09-20
Date Acceptance
2022-09-07
Citation
Nature Communications, 2022, 13, pp.1-10
ISSN
2041-1723
Publisher
Nature Research
Start Page
1
End Page
10
Journal / Book Title
Nature Communications
Volume
13
Copyright Statement
© The Author(s) 2022. Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as
long as you give appropriate credit to the original author(s) and the
source, provide a link to the Creative Commons license, and indicate if
changes were made. The images or other third party material in this
article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not
included in the article’s Creative Commons license and your intended
use is not permitted by statutory regulation or exceeds the permitted
use, you will need to obtain permission directly from the copyright
holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as
long as you give appropriate credit to the original author(s) and the
source, provide a link to the Creative Commons license, and indicate if
changes were made. The images or other third party material in this
article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not
included in the article’s Creative Commons license and your intended
use is not permitted by statutory regulation or exceeds the permitted
use, you will need to obtain permission directly from the copyright
holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
Identifier
https://www.nature.com/articles/s41467-022-33207-x
Grant Number
BB/R002614/1
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
PROTEIN-COUPLED RECEPTOR
CANNABINOIDS
IDENTIFICATION
LIGAND
Biosensing Techniques
Cannabinoids
Dronabinol
Humans
Pheromones
Saccharomyces cerevisiae
Workflow
Humans
Saccharomyces cerevisiae
Cannabinoids
Pheromones
Biosensing Techniques
Workflow
Dronabinol
Publication Status
Published
Article Number
5509
Date Publish Online
2022-09-20