'Think of yeast as a factory...' Microbial fermentation can deliver CBD with consistent purity at a lower cost, says Demetrix

It also uses less land, water and energy, and enables firms to produce rarer cannabinoids it would not be commercially viable to extract from plants, Jeff Ubersax, PhD, CEO at Emeryville-CA-based Demetrix​​ told FoodNavigator-USA.

“There is room for both types of products on the market, but the industry is facing a supply challenge as it looks to agriculture as its only source of supply ​[for cannabinoids]," claimed Ubersax, a molecular biologist and former VP of R&D at Amyris, which is also developing cannabinoids via fermentation.​​

"There are more than 100 cannabinoids in the cannabis plant but only a few of them are really accessible through agriculture and we think there are other cannabinoids ​[in addition to CBD] that are going to have a lot of promise. ​

“We also have the ability to make new-to-nature cannabinoids, where we can feed kind of precursors to the cannabinoids to a yeast cell, and the yeast cell will take those up and incorporate them into a cannabinoid chemical scaffold to make all sorts of new to nature cannabinoids which we think could be important for pharmaceutical applications.”​

Competitive advantage​

A growing number of firms are using genetically engineered yeast to biosynthesize cannabinoids by effectively reverse engineering how Cannabis sativa​ plants make these molecules​​, he said.

However, Demetrix, which deploys technology developed by cofounder and synthetic biology pioneer Dr Jay Keasling at the UC Berkeley (that was recently referenced in a paper in​ Nature​​) ​has a strong head-start, he claimed.

Think of yeast as a factory…​

“Think of yeast as a factory,” ​said Ubersax, who has raised $11m in a seed round led by Horizon Ventures and is currently raising an undisclosed sum for a Series A round.

“DNA is like a blueprint for all the different pieces of equipment in that factory that are required to make the final products. We’re taking some DNA parts from cannabis plants and re-coding them and then putting them in yeast to make that yeast factory produce new things.”​

He added: “The cannabis plant was sequenced in the early 2000s and people I think thought that they had all the parts from the plant that they needed to put into the yeast cell to have the yeast produce all those cannabinoids. But the fact was, it didn’t actually make very much.   ​

“So if you think of all the parts you need ​[to make yeast produce cannabinoids], there was one particular part we used before that was like the engine of a small compact car. ​

“Jay’s lab said this is not working really well, so they went back to the plant to see if there were other parts that had been missed, and they found a part that looks a lot more like a jet engine. They put that in the yeast factory, and all of a sudden they were making commercially interesting amounts ​[of cannabinoids].

“But as you might also imagine, if you put a jet engine in a factory that’s not designed for it, a lot of other things break, so we’ve spent the last year working to make other changes to the yeast cell and some of those other parts we’ve brought into it to keep up with that jet engine.”​

Faster and more flexible

He added: “The IP that came out of Jay’s lab at Berkeley was a big missing step in the cannabinoid pathway and was really one of the big bottlenecks... So when Demetrix was set up, one of our first goals was to get an exclusive license to that IP out of Berkeley, and we think this will give us a significant advantage, as others will have to figure out creative ways to make that same step work.​

"We are incorporating a bunch of technologies that didn't even exist when companies such as Intrexon, Amyris or Gingko Bioworks started to build their capabilities, so we can be faster and more flexible." ​

A world-class team​

Aside from the technological breakthroughs made by Dr Keasling's team, he said, “We’ve also recruited a team of industry veterans​​ who have had experience of commercializing natural products in yeast, and we’ve had a large seed round that has allowed us to expand and hire more people ​[the team now includes 23 people]. ​

“We also have world class ​[facilities] that will allow us to move very quickly towards commercialization.”​

Isolated cannabinoids vs broad or full spectrum hemp extracts​

Many brands promoting CBD right now are using hemp extracts (which contain CBD and other cannabinoids), in part because they feel they are on safer legal ground as the FDA says CBD is illegal in foods & supplements, but has not opined on extracts specifically (read more about the FDA's position on CBD HERE​​).

However, they also cite the so-called 'entourage effect,’ arguing that there are benefits from the synergistic interaction of the cannabinoids, flavonoids, terpenes, and fatty acids in a full spectrum extract as opposed to CBD alone.

In reality, claimed Ubersax, much of this is conjectural given the lack of research, he said. “It’s not been particularly well studied.”​

Fermentation, he said, allows firms to produce a variety of high purity single molecules and accurately determine which ones have beneficial effects. “We think this is especially important from a safety and efficacy perspective. Single molecules really let you do the high quality studies you need to prove they are safe and effective.”​