"it Worked Like Gangbusters“- Cannabinoids Grown From Yeast

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Greetings farmers,

It’s been recently announced that synthetic biologists have created an enzymatic network in yeast that turns sugar into cannabinoids, including tetrahydrocannabinol and cannabidiol, but also novel cannabinoids not found in the marijuana plant itself. This includes the possibility of new therapies based on novel cannabinoids: the rare ones that are nearly impossible to get from the plant, or the unnatural ones, which are impossible to get from the plant.

For the consumer, the benefits are high-quality, low-cost CBD and THC: you get exactly what you want from yeast.

Cannabinoids join many other chemicals and drugs now being produced in yeast, including human growth hormone, insulin, blood clotting factors and recently, but not yet on the market, morphine and other opiates.

"It was an interesting scientific challenge," he admitted, that was akin to other challenges he and his team have successfully overcome in yeast: producing an antimalarial drug, artemisinin; turning plant waste into biofuels; synthesizing flavors and scents for the food and cosmetics industries and chemical intermediates for making new materials.

"But when you read about cases of patients who have seizures and are helped by CBD, especially children, you realize there is some value in these molecules, and that producing cannabinoids in yeast could really be great."

The researchers ended up inserting more than a dozen genes into yeast, many of them copies of genes used by the marijuana plant to synthesize cannabinoids.

One step, however, proved to be a roadblock for Keasling's group and competing groups: an enzyme that performs a key chemical step in making CBGA in the marijuana plant didn't work in yeast.

Rather than engineer a different synthetic pathway, Berkeley postdoc Leo d'Espaux and graduate student Jeff Wong went back to the plant itself and isolated a second enzyme, prenyl transferase, that does the same thing, and stuck it in the yeast.

"It worked like gangbusters," Keasling said.

Berkeley postdoc Xiaozhou Luo and visiting graduate student Michael Reiter, who led the project, started assembling in yeast a series of chemical steps to produce, initially, the mother of all cannabinoids, CBGA (cannabigerolic acid). In both marijuana and yeast, the chemical reactions involve the acid form of the compounds: CBGA and its derivatives, THCA and CBDA. They readily convert to CBG, THC and CBD when exposed to light and heat.

They also added enzymes that made the yeast produce two other natural cannabinoids, CBDV (cannabidivarin) and THCV (tetrahydrocannabivarin), whose effects are not well understood.

Surprisingly, Xiaozhou and Michael discovered that the enzymatic steps involved in making CBGA in yeast are flexible enough to accept a variety of starter chemicals -- different fatty acids in place of the one used by the marijuana plant, hexanoic acid -- that generate cannabinoids that do not exist in the plant itself. They also got the yeast to incorporate chemicals into cannabinoids that could later be chemically altered in the lab, creating another avenue for producing never-before-seen, but potentially medically useful, cannabinoids.

“The economics look really good," Keasling said. "The cost is competitive or better than that for the plant-derived cannabinoids. And manufacturers don't have to worry about contamination -- for example, THC in CBD -- that would make you high."

To learn more check out the “Complete biosynthesis of cannabinoids and their unnatural analogues in yeast” In the journal of nature. Or do a google search for “Cannabinoids from yeast”.

Who knows, in a couple of years producers may be manufacturing THC similar to how beer is brewed. You’ll pick up 5-hour CBD energy and a 6 pack of Kush-lite rather than a jar of cured flowers. Instead of growing roadkill skunk, you’ll be synthesizing the most pungent pure isolated skunk terpenes in yeast.

Personally I think it’s created a solution to a problem that didn’t exist. Why does the world need more cheap synthetic opioids and THC analogues? I can only imagine the consequences when the mafia and cartels get involved.

Herbal Cannabis contains 100 different compounds such as major canabinoids (THC, CBD, CBN, etc), minor canabinoids, terpenes and flavonoids that all interact in synergy within the human body in ways that are still being researched (entourage effect). To think that you can pick out a handful of canabinoids and leave the rest seems a bit overly simplistic.
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