Genetically modified yeast produces cannabinoids


Produce cannabinoid components without cultivating cannabis?

Researchers at the University of California have successfully produced cannabinoid components in the laboratory from yeast. Producing cannabinoids without growing marijuana could be of interest to pharmaceutical companies wanting to add these ingredients to their products in the future.

By hacking the biology of yeast, scientists have found a way to make the active ingredients of the cannabis plant. Manipulated microorganisms produce THC, CBD and cannabis cousins ​​that are rare and less well understood.

Saccharomyces cerevisiae

If you had to choose a favorite microbe, the Saccharomyces cerevisiaewould be a good candidate, better known as brewer's yeast, which turns grape juice into wine, cereal puree into beer and dough into bread. In recent decades, scientists have manipulated the genome of yeast to produce hormones such as insulin and drugs like opioids. Today, he produces cannabinoids.

Researchers led by Jay Keasling, professor of chemical engineering and bioengineering at the University of California at Berkeley, manipulated genetically modified beer yeasts to produce two of the most common cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). They claim that their method could also
generate micro-organisms capable of producing other naturally occurring cannabinoids as well as brand new varieties. Some cannabinoids can be used to treat various disorders, but more research is needed to distinguish the hype from medical reality.

This technique is not new: the genetically modified yeast has already been used to make hops to give the flavor of beer, synthetic egg whites, and even chemicals to flavor chocolate.


In the new study published Wednesday in Nature, scientists have transferred into the yeast known genetic sequences that control the metabolic pathways of hemp plants. The resulting microorganisms can transform a sugar called galactose into chemical intermediates and use these chemicals to synthesize cannabigerolic acid (CBGa), the mother cannabinoid that can be converted into several other compounds. Finally, each strain of yeast transforms CBGa into a different cannabinoid.

"The yeast that produces THC is different from the yeast that produces CBD, but it only differs in one gene - and it is this last gene that turns CBGa into CBD or THC," says Keasling. "The beauty of this technology is that you can trade them for a rare cannabinoid."

The researchers used a technique called "synthetic biology" to identify an enzyme called CsPT4. With this enzyme and based on DNA analysis of the cannabis plant, they will produce the components of cannabis.

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In this case, the team gave their yeast a gene derived from cannabis that contains instructions for the production of olivetolic acid, a precursor compound of THC or CBD. They also gave them cannabis genes that would create the enzymes that could turn ololeic acid into THC and CBD. Thus, in addition to a regular galactose-based diet, the yeast had everything needed to meet the demands of the team.

"Together, the team writes, these results lay the groundwork for large-scale production of natural and synthetic cannabinoids, which could improve pharmacological research on these compounds.

Cannabis contains more than 100 cannabinoids different, but most of them are at much lower concentrations than CBD and THC, some are even unknown. Because plants produce very small amounts of rare substances, they are more expensive to produce. Even when researchers are able to extract them, the compounds are often contaminated with traces of their most common cousins. Yeast could produce purer versions of these cannabinoids, which would bring the price of rare varieties to the same level as the most popular ones. "It's a platform to produce all the cannabinoids that are currently thought to exist in cannabis as well as all those that are unnatural and not found in any organism," says Keasling. What makes some of these "unnatural"? Normally, hemp plants incorporate a chemical called hexanoic acid (which humans use as a cheap food additive) in cannabinoids. When the Keasling team added various chemicals to the yeast's sweet diet, the genetically engineered microbes incorporated these substances instead of hexanoic acid, resulting in new compounds never seen before.


To discover potential medical applications will require much more research - and scientists are already busy studying the effects of the most famous cannabinoids.

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To find the true applications of compounds, researchers must test how cannabinoids affect humans. It is a problem that this new method of biosynthesis may not solve. "It does not matter if the CBD or the cannabinoids come from a plant or if they are made synthetically or if they come from yeast. If the end product is still a banned substance, it does not increase accessibility, "says Yasmin Hurd, director of the Institute of Addiction at Icahn School of Medicine in Mount Sinai, New York, which does not participated in this new study.

Mr. Keasling agrees that, despite the easing of state laws, federal restrictions on cannabis testing make research difficult - "and there is no way around this problem until the law is passed. modified, "he says. "But this method can provide some of these very rare cannabinoids that you could never extract from cannabis because they are produced in such small amounts. And who knows, one of them could be better than CBD or THC. "


Whether they contribute to research or not, yeast cannabinoids will certainly have a commercial impact. Keasling estimates that his method could produce cannabinoids at a cost equal to or less than that of agricultural marijuana production. He founded Demetrix to license his new Berkeley technology and develop commercial cannabinoid production. And he has a lot of competition. Last year, biotech start-ups Librede and Gingko Bioworks announced a patent for the production of CBD from yeast, respectively, and a multi-million dollar partnership with the cannabis company Cronos Group. Jeff Ubersax, CEO of Demetrix, believes that about 15 at 20's other companies are competing to turn yeast cells into small cannabinoid plants.

The goal of this study was to find how to produce cannabinoids "regardless of cannabis culture"; in other words, reap the benefits without needing the plant. There is a big advantage to doing this: The cannabinoids currently used for prescription drugs like Epidiolex, are derived directly from the plant, where they do not really exist in very high concentrations. If the same compound can be produced artificially, it will be much easier to scale it up to make prescription drugs.

Tags : ADNbeerbiotechnologyGeneticR&D