Beyond Bud: Meet the Leaf-free Future of Cannabis Production

In many ways, cannabis culture is a horti-culture. Those who cultivate the plant prize their “green fingers,” the regions that legalize its use are known as “green states,” and all keen cannabis entrepreneurs live by the same motto: “go get the green.” 

But as the cannabis industry grows and modernizes, its future might not be so viridescent. 

In recent years, several high-profile pharmaceutical companies have taken an eager interest in this once clandestine sector. Seeking to co-opt the plant’s cannabinoid compounds into a range of medicines and cosmetics, the companies could be cannabis’ largest endorsers for mainstream commercial acceptance. Except these industrial giants aren’t interested in gardening. 

“I think that is a process to try 100 years ago, but not in the 21st century,” says Patrick Schmitt, chief scientific officer and co-founder of Farmako GmbH, a German pharmaceutical company. 

Back in February this year, Farmako applied for a worldwide patent for its unique cannabinoid-producing process, one that favours microorganisms over marijuana. The company boast that its bio-bacteria method slashes cannabinoid production costs to one-thousandth of its competitors’ overheads. But, for Schmitt and the company’s other champions, Farmako’s biggest selling point is its modernizing ambition. 

“So there's a high demand for cannabinoids,” he says. “But, for a plant, you need a lot of space, you need a lot of water, you have to build up greenhouses, and you have to cultivate lands under GMP [good manufacturing practices] conditions for medical users. I just think the whole process doesn't match the possibilities we have today from technology.”

For Farmako, the future of cannabis isn’t green. Nor is it leafy, floral, or agricultural in any nature. The future is synthetic. And it’s one with precedent in other plant products. 

“So today, nobody expects vitamin C from lemons, for example,” says Schmitt. “It's now bio synthetically produced.”

And like its citrusy counterpart, Farmako’s own synthetic method rests on the actions of bacteria, which, quite fittingly, could go down well with a slice of lemon. Zymomonas mobilis, also known as the tequila bacteria, is a microbe commonly used in the production of tequila and African palm wine. But instead of converting sugar into alcohol, Schmitt and his team at Farmako genetically modified the bacteria to turn out cannabinoids. 

“You have to modify several genes, which are coding for several enzymes,” Schmitt explains. “And these enzymes catalyze different chemical reactions which lead at the end to the final product, which in our case is CBD or other cannabinoids.” 

Remarkably, the team claim that their genetic control over Zymomonas cannabinoidis – their inspired name for the genetically altered Z. mobilis bacteria – is so precise that they can modify the microbe to produce over 150 different cannabinoids with just a simple gene switch. “We have to change just one single gene in the bacteria,” Schmitt continues. “Then we have a different strain which produces THC, and the other one produces CBD. So, engineered like that, we can actually engineer 180 different bacterial strains, and each is able to produce another cannabinoid in high purity.”

But to anyone attentive to the cannabis industry, the whole process may feel very familiar. Back in February of this year, researchers from the University of California, Berkeley, announced that they had engineered brewer's yeast to convert sugar into THC, CBD, and “novel cannabinoids not found in the plant itself.” On the surface, the method may seem identical to Farmako’s, but Schmitt is no fan of a comparison.  

“It's not bacteria, it’s fungi,” he clarifies. “Which means it’s a eukaryotic organism, which means you'll have many different troubles in the synthesis of natural substances.”

“Imagine you want to tune a new car with a lot of electricity and put a lot of technology stuff inside,” he continues. “It would be easier to modify a car from the 1920s or something which hasn't that much technology, so everybody could do it. And it’s the same case in eukaryotic and prokaryotic organisms. So the prokaryotic organism, which includes bacteria like our Zymomonas, would be the old car, which hasn't that much technology stuff on it and it's pretty primitive, so pretty easy to modify.” 

In other words, bacteria’s simplicity is its strength. As a more primitive cell compared to yeast, Z. cannabinoidis is far easier to refit for new purposes. And its bacterial benefits don’t stop there. According to Schmitt, it’s also the least messy of the two microbes. 

“Even though cannabinoids are created inside these [yeast] cells, they can't go out into the media,” he explains. “That means the yeast cell has to be broken up, so you have to stop the process to kill all the cells in your bioreactor to get the product out. Then empty the bioreactor, clean it, and fill it new.”

“Our bacteria has a specific advantage: it spits out the cannabinoids into the outer medium,” he adds. “So we can have way higher amounts because there are no limits in the production process.”

And these high amounts of cannabinoids are exactly what Germany needs. Despite legalizing the medical use of cannabis back in March 2017, doctors’ conservatism, supply chain issues, and pharmacy shortages have combined to keep cannabis out of the hands of the patients who need it. And while the German Federal Institute for Drugs and Medical Devices recently awarded its first round of cannabis cultivating contracts to several companies, the first harvest isn’t expected until late 2020. Until then, Farmako’s bacteria-brewed cannabis might be the best bet for the patients desperate for treatments and the cannabis researchers desperate to develop them.

“I think our biosynthetic process we will be the leader of the European market because we are the only ones with access to these cannabinoids in high amounts and that opens of course the gates for doing research on them in clinical studies and formulating medicinal products,” says Schmitt. 

“Because we want to do a research. So why is CBD, for example, suitable for epilepsy and pain relief? I think this will be only possible if we can produce cannabinoids in high yields. Otherwise, there is no possibility to do this research.”