Screening microbially produced Δ9-tetrahydrocannabinol using a yeast biosensor workflow
Autor: | Shaw, William M, Zhang, Yunfeng, Lu, Xinyu, Khalil, Ahmad S, Ladds, Graham, Luo, Xiaozhou, Ellis, Tom |
---|---|
Přispěvatelé: | Khalil, Ahmad S [0000-0002-8214-0546], Ladds, Graham [0000-0001-7320-9612], Ellis, Tom [0000-0001-5392-976X], Apollo - University of Cambridge Repository, Biotechnology and Biological Sciences Research Council (BBSRC) |
Rok vydání: | 2022 |
Předmět: |
Multidisciplinary
Science & Technology IDENTIFICATION Cannabinoids article General Physics and Astronomy General Chemistry Biosensing Techniques Saccharomyces cerevisiae 140/58 General Biochemistry Genetics and Molecular Biology Pheromones Workflow Multidisciplinary Sciences PROTEIN-COUPLED RECEPTOR 631/92/552 631/1647/350/59 38/35 Science & Technology - Other Topics 631/61/318 Humans Dronabinol LIGAND 631/1647/334/2243/1796 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |