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:
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