“Hey, man.”
“Yeah, what?”
“You know how you’ve got craft beer, right?”
“Yeah, I guess.”
“Well, imagine if — imagine if it was possible to brew cannabis like you brew beer.”
“That would be awesome. Someone should totally come up with that.”
The above conversation, no doubt set to a background of contemplatively munched pizza and roots reggae, sounds like your typical 1:00am conversation among first year college students. It’s the kind of idea that sounds brilliant in the wee hours of the morning; it’s the kind of idea that, if remembered at all, sounds entirely impossible in the cold light of day.
Yet despite how far-fetched it might sound, someone — or rather a team of someones — has pulled it off. At the University of California, Berkeley, synthetic biologists have managed to engineer brewer’s yeast so that it produces the main cannabinoids found in marijuana: mind-altering THC and the non-psychoactive CBD. Fed only on a diet of sugar, this yeast represents an easy and far cheaper way to produce cannabinoids than is otherwise on offer today.
“We wanted to produce cannabinoids in a better way,” Jay Keasling, a UC Berkeley professor of chemical and biomolecular engineering and bioengineering, told Digital Trends. “We took the genes out of cannabis that are responsible for making cannabinoids and combined them with genes from other organisms into brewer’s yeast. The entire process is as simple as brewing beer, except rather than having the yeast make ethanol it makes cannabinoids.”
Aiming high
We’ll stop short of likening Keasling’s journey from respected educator to drug mastermind to the plight of Breaking Bad’s Walter White. Certainly, it doesn’t involve any of the criminality. But it’s nonetheless a tale of how a brilliant chemist can lend their expertise and unique insights to totally change the way we create what (until far too recently in the case of marijuana) was an illicit high. In short: move over weed connoisseurs, there’s a new sheriff in town!
“This is the kind of work that my lab has been doing for decades,” he said. “A little over 10 years ago, we took the genes out of a plant called wormwood and put them into yeast, and then got that yeast to produce the precursor to an antimalarial drug called artemisinin. Artemisinin is normally extracted from wormwood, and we managed to get yeast to produce it.”
This exciting effort was followed by myriad other molecules over the following decade, produced using a similar microbial approach. Then cannabis legalization happened and, with it, a whole new opportunity presented itself. “When we saw that there was interest in cannabinoids, and that the pathway that is naturally found in cannabis had been elucidated, we started to put it into yeast,” he said. “We were very fortunate to get it to work.”
To understand how significantly different the team’s approach is, it’s necessary to consider how cannabinoids are traditionally produced — and what is wrong with this approach. This process involves physically growing cannabis plants, either in a field or in a greenhouse. Once grown, a process which takes several months, those wanting to extract cannabinoids do so by harvesting buds from the plant.
Keasling explains that there are several ways in which his team’s new method makes sense as an alternative. For one thing, it’s cheaper and addresses environmental concerns. In California, cannabis cultivation is responsible for an estimated 3% of electricity usage, resulting from the large quantities grown indoors. Other states have experienced a significant increase in electricity demand after legalizing recreational cannabis. In Colorado, half of the load growth on the grid has been attributed to cannabis cultivation. There’s also a huge amount of waste involved. The buds of a cannabis plant are a relatively small part, but the rest of the plant nonetheless needs to be grown and then (more importantly) disposed of by farmers.
“You don’t want to burn it because it harms the atmosphere,” Keasling said. “With fermentation you have much less waste and much less energy use.”
Oh, yes, did we mention the cost? According to Keasling, the yeast cost involved in his team’s microbial approach to growing is around one-tenth the cost of producing cannabinoids in open fields, and an even bigger saving versus growing them indoors. Its biggest saving of all is when compared to the existing process of chemically synthesizing cannabinoids, something that is used to produce certain FDA-approved drugs. “That’s super expensive,” he said. “It costs around $40,000 to $70,000 per kilogram to produce those molecules using chemical synthesis. With yeast fermentation, we can produce them for about $400 per kilogram.”
New blockbuster drugs
Another enormous advantage is the access to pure cannabinoid molecules. “When you grow cannabis, depending on the variety, you get THC predominantly, with a bunch of other cannabinoids in minor levels,” he explained. “Or you get CBD, plus a bunch of other cannabinoids. You then have to purify it. With the yeast, we can produce nearly pure CBD or THC.”
This is potentially invaluable when it comes to the use of cannabis extracts, such as THC, which is used in everything from recreational edibles to medicines able to reduce nausea after chemotherapy or improve appetite in patients with HIV. CBD, meanwhile, is increasingly used in cosmetics (often termed “cosmeceuticals”.) It has also been explored as a possible therapeutic solution for conditions such as Parkinson’s disease and chronic pain.
“There are all these different ways to get cannabinoids,” Keasling said. “You can get CBD oil. You can get edibles. But no-one really knows how much is really in those, outside of their claims. Now we have the possibility of getting exact doses of molecules of interest. There’s no more guesswork involved. And you won’t have to worry about contamination of other molecules.”
The yeast-based approach opens up the possibility of studying these lesser-known marijuana components.
Things go beyond THC and CBD, too. There are more than 100 other chemicals in marijuana. However, extracting them for study has proven difficult because they are produced in such tiny quantities. The yeast-based approach opens up the possibility of studying these lesser-known marijuana components.
“With this platform, you take the synth base which makes the particular cannabinoid that you want and you graft it into the yeast that produces the precursor to those cannabinoids,” he said. “You can then produce any of the 100 molecules that you want.”
It is possible, Keasling continued, that there might be “blockbuster drugs” in these other cannabinoids that are simply too “rare to have been studied” up until now.
A budding industry
“It’s going to be interesting to see how all of this plays out over the next few years,” Keasling said, on the topic of the continuing debate around marijuana legalization in the United States — and the world at large. “I would predict that there will be many more countries and U.S. states that will be legalizing recreational use of cannabinoids. It’s a really interesting time.”
If he’s right (and, heck, whatever else you can say about 2019, it can never be accused of being boring), then he’s in the right place to take advantage of it. The work of Keasling’s lab is currently in the process of being commercialized. He is the co-founder of a synthetic biology called Demetrix, which is working to develop this research into actual products.
“The company has 20 people,” he said. “We are working on improving the original yeast that we built. There’s now a yeast that works much better than the one reported in [our original paper]. It produces much higher quantities. I would say in the next two to three years we’ll have products out on the market from this process. [The company] is looking at both FDA-approved therapeutics and therapeutics that could be FDA-approved, as well as going into the cosmetic and nutraceuticals markets — and maybe even into the recreational market as well. I think it has broad commercial applications.”
But does this mean the end of the humble marijuana grower as we’ve known them? Don’t bank on it.
“I think there are still going to be a lot of people who want the ‘natural experience,’ let me put it that way,” he said. “It’s clear that there are also a lot of other components in cannabis — terpenes, flavors, fragrances — that give you that. Those may be challenging to replicate in the yeast fermentation process. I don’t expect that it will completely replace the plant process. But I do think that, for a number of applications, plants won’t be used. For example, for cosmetics companies that want to put CBD into skin creams, this will be the go-to way. The same might be true for CBD sport drinks or beer. Yeast fermentation means they’ll be able to know exactly what they’re putting in. But there will still be people who want to smoke marijuana — and they’ll always be a place for that.”
