期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-33207-x
关键词
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资金
- National Key Research and Development Programme of China [2018YFA0903200]
- URKI Biotechnology and Biological Sciences Research Council (BBSRC) [BB/M503381/1, BB/R002614/1]
- National Science Foundation (NSF) [CCF-2027045]
- Department of Defence (DoD) Vannevar Bush Faculty Fellowship [N00014-20-1-2825]
- W.M. Keck Foundation
The study developed a yeast-based biosensor for screening microbial mutant libraries producing Delta 9-THC, aiming to improve production efficiency. Utilizing the cannabinoid biosensor, THC can be detected in microbial cell culture, providing a new tool for screening high producers.
Microbial production of cannabinoids promises a cheaper and more sustainable route to these important therapeutic molecules, but strain improvement and screening is challenging. Here, the authors develop a yeast-based Delta 9-tetrahydrocannabinol (THC) biosensor for screening microbial mutant libraries. 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.
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