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Screening microbially produced Δ9-tetrahydrocannabinol using a yeast biosensor workflow.

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Shaw, William M 
Zhang, Yunfeng 
Lu, Xinyu 


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.



Article, /631/61/318, /631/92/552, /631/1647/350/59, /631/1647/334/2243/1796, /38/35, /140/58, article

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Nat Commun

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Springer Science and Business Media LLC
RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (BB/M503381/1, BB/R002614/1)