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Brewing cannabinoids in yeast

Thursday 28 Feb 19

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Jay Keasling
Scientific Director
DTU Biosustain

Several chemical compounds found in cannabis (cannabinoids) have now been produced by genetically modified yeast, reports a paper published in Nature. This finding can potentially lead to improved and environmentally friendly therapeutic cannabinoids.

In a new Nature paper, a group of researchers report successful production of chemical compounds present in cannabis (cannabinoids) by genetically modified yeast. This work could lead to efficient production of different types of cannabinoids, independently of cannabis cultivation.

According to Principle Investigator and Professor of Chemical and Biomolecular Engineering at UC Berkeley Jay Keasling, producing cannabinoids by fermentation allows for better control and less waste. Today, production of cannabinoids requires huge amounts of farm land and generates a lot of plant waste.

The microbial production process will produce less waste, which is good for the environment. Also - anyone can grow a plant, but we can build dependencies and kill-switches into yeast that could prevent the average Joe from growing it. So, producing cannabinoids in yeast will both make the production of these compounds greener and safer,” says Jay Keasling, who is also Scientific Director at The Novo Nordisk Foundation Center for Biosustainability at Technical University of Denmark (DTU). 

Great potential as therapeutics

Specific cannabinoids have been approved as prescription drugs in several countries for treating various illnesses. Cannabinoids are currently derived from the cannabis plant, where they are found at relatively low abundance. This, in addition to their chemical complexity, has hampered the large-scale production of cannabinoids. 

"Producing cannabinoids in yeast will both make the production of these compounds greener and safer"
Jay Keasling, Scientific Director at The Novo Nordisk Foundation Center for Biosustainability at Technical University of Denmark (DTU Biosustain).

Jay Keasling and colleagues genetically modified brewer’s yeast (Saccharomyces cerevisiae) to produce cannabinoids via biosynthesis. The authors introduced cannabis genes into the yeast’s metabolic pathways to produce cannabinoid precursor molecules, such as olivetolic acid, from the simple sugar galactose. From olivetolic acid, the yeast was able to produce the key cannabinoid cannabigerolic acid (CBGA), which could in turn be used to produce Δ9-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). 

Brewing cannabinoids is much cheaper

The authors also showed that this production route is much cheaper than growing marijuana plants for extraction of for instance Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for therapeutic purposes.

Today, open field production gives a cost of 40,000-70,000 Dollars/Kg for these chemicals. From previous work with microbial production of artemisinin – an anti-malaria drug compound – the researchers expect to be able to produce cannabinoids at less than 400 Dollars/Kg.

The scientists also demonstrated that synthetic cannabinoids, such as chemically modified THCA, could be produced from fatty acids instead of galactose. Together, these results lay the foundation for the large-scale production of both natural and synthetic cannabinoids, which could improve pharmacological research into these compounds.

“The microbial process allows us to produce cannabinoids that are extremely rare in the plant. Further, we can make the yeast produce “unnatural” cannabinoids that nature cannot produce itself, which gives us many new possibilities of developing new therapeutics,” says Jay Keasling.

CONTACT

Jay Keasling (University of California Berkeley, Berkeley, CA, USA)

E-mail: keasling@berkeley.edu

Resources

http://dx.doi.org/10.1038/s41586-019-0978-9

DOI: 10.1038/s41586-019-0978-9

Press release from University of California Berkeley: https://chemistry.berkeley.edu/news/yeast-produce-low-cost-high-quality-cannabinoids

Nature: https://www.nature.com/articles/d41586-019-00714-9