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Genetically modified yeast produces cannabinoids

processing brewer's yeast

Produce cannabinoid components without cultivating cannabis?

Researchers at the University of California have successfully produced cannabinoid components from yeast in the laboratory. Producing cannabinoids without growing cannabis could be of interest to pharmaceutical companies keen 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.

University of California, Saccharomyces cerevisiae, Jay Keasling, genetically modified yeast
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 such as opioids. Today, it produces cannabinoids.

Researchers led by Jay Keasling, professor of chemical and bioengineering at the University of California at Berkeley, manipulated genetically engineered brewer's yeast to produce two of the most common cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). They claim that their method could also
generate microorganisms capable of producing other naturally occurring cannabinoids as well as completely new varieties. Some cannabinoids can be used to treat a variety of disorders, but more research is needed to distinguish the hype from the medical reality.

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

Experience

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

“Yeast that produces THC is different from yeast that produces CBD, but they differ only in one gene - and it is this latter gene that turns CBGa into CBD or THC,” Keasling explains. “The beauty of this technology is that they can be traded in for a rare cannabinoid. "

University of California, Saccharomyces cerevisiae, Jay Keasling, genetically modified yeast

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

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

Together, the team writes, “these results lay the groundwork for the 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. Since plants produce very small amounts of rarer substances, they are more expensive to produce. Even when researchers succeed in extracting them, the compounds are often contaminated with traces of their more common cousins. Yeast could produce purer versions of these cannabinoids, which would bring the price of rare varieties to the same level as the more 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,” Keasling says. What makes some of these “unnatural”? Normally, hemp plants incorporate a chemical called hexanoic acid (which humans use as a cheap food additive) into cannabinoids. When Keasling's team added different chemicals to the yeast's sweet diet, genetically engineered microbes incorporated these substances instead of hexanoic acid, resulting in new compounds never seen before.

PUTTING CANNABINOIDS TO THE TEST

Uncovering potential medical applications will require a lot more research - and scientists are already busy studying the effects of the most famous cannabinoids.

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To find the compounds' true applications, researchers need to test how cannabinoids affect humans. This is a problem that this new method of biosynthesis may not solve. “It doesn't matter if CBD or cannabinoids come from a plant or if they are made synthetically or if they come from yeast. While the end product is still a banned substance, it doesn't increase accessibility, ”says Yasmin Hurd, director of the Institute of Addiction at the Icahn School of Medicine in Mount Sinai in New York City, who did not participated in this new study.

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

GROWING INDUSTRY

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

The goal of this study was how to produce cannabinoids “independent of growing cannabis”; in other words, to reap the benefits without needing the plant. There's a big plus to doing this: The cannabinoids currently used for prescription drugs like Epidiolex, are derived directly from the plant, where they don't actually 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.


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