Yeast fermentation will be the reply to the emergence of uncommon cannabinoids
Celia Gorman May 19, 2020
(nordroden / AdobeStock)
From a purely chemical perspective, a cannabinoid is a cannabinoid and a THC molecule is a THC molecule, regardless of how it is produced, whether in a laboratory or on a farm. From a legal perspective, a cannabinoid is a cannabinoid – at least in Canada. The production and distribution of CBD are subject to the same standards as the psychoactive compounds in cannabis.
In the USA, however, THC and CBD differ legally. After the 2018 Farm Bill was passed, hemp and cannabis with an extremely low THC content – less than 0.3% – became legal nationwide. While non-psychoactive cannabinoids can act, look and croak like ducks, they could turn out to be swans.
This opportunity has prompted researchers and companies to take advantage of the medical opportunities and potential benefits of the less common cannabinoids in cannabis plants. These rarer cannabinoids occur in such small amounts that it is impractical to extract large amounts from marijuana plants. But a little bit of genetic engineering, a lot of research, and a few metal tanks full of yeast bacteria could enable mass production.
The race for rare cannabinoids
Yeast fermentation is an ancient process that is known to most as a source of beer or bread. However, it is known in the scientific community as one of the primary bacteria used to make biopharmaceuticals (the other is E. coli).
Today the scientific race is underway to investigate specific cannabinoids other than THC or CBD for the treatment of diseases such as epilepsy. And the commercial breed is in the process of making these cannabinoid research facilities available.
From a researcher's perspective, it doesn't matter how the cannabinoid is made. Consistency and reliability of care are required, not sunlight and dirt. While yeast must be genetically engineered to produce a cannabinoid, the end product is genetically identical to its herbal counterpart.
Although there are no safety or efficacy concerns, the origin of the substances can play a role from a consumer perspective – if you know about them. Once cannabinoids are harvested and refined into an oil, it is impossible to tell whether they come from a plant or a test tube. They all croak like ducks.
Production of cannabinoids by yeast fermentation
"There's so much to explore. We're just getting started," said Cynthia Bryant, chief business officer at Demetrix, a US company that focuses on the potential medical benefits of non-psychoactive cannabinoids for the US American pharmaceutical market.
Demetrix, based in California, is working on large-scale cannabinoid production outside of agriculture. And they believe yeast fermentation will get them there.
"The technology works very well to make a rare cannabinoid," said Bryant. Once operational, they can quickly and regularly produce large amounts of specific cannabinoids, building a supply chain that is reliable enough for pharmaceutical research and pharmaceuticals. The sale could include oils and crystallized powders for research, clinical trials and finally as active ingredients in medicines.
Over a hundred different cannabinoids can be extracted from cannabis plants, but many exist in such small amounts that they have never been studied as isolated medicinal ingredients.
Demetrix has identified the first so-called rare cannabinoid to be launched on the market. Bryant would not name the specific cannabinoid the company plans to launch next year, citing trade secrets, and only said that they "discovered some useful effects."
The yeast fermentation process
Insulin, the first biopharmaceutical, was once extracted from pig pancreas. In the late 1970s, scientists cloned the gene that makes the human body produce insulin, cut a piece of DNA out of a yeast cell, and put the manipulated gene in its place. Instead of producing alcohol, the yeast cells became tiny factories that produced insulin.
Suddenly, it was exponentially easier and cheaper to make insulin. The new method was fast, consistent, and scalable so that it could be replicated at the commercial level. It is also completely safe. Today's yeast fermentation process is similar, if significantly advanced.
Demetrix-Versandhandel produced synthetically generated DNA sequences of the enzymes in cannabis, which were identified as instigators of natural cannabinoid production. The scientists then insert the DNA sequence into yeast cells and reprogram their purpose. The specific methods used vary from company to company and are considered business secrets. However, the general procedure for using a microorganism to produce a particular molecule is common throughout the field.
The modified yeast cultures are then fermented and grown in tanks, with large amounts of the desired cannabinoid being propagated and produced. The workers then extract the cannabinoids from the yeast slurry, isolate and purify them.
"I think there will be a great need for these cannabinoids," said Bryant. The more cannabinoids are examined, the more medical solutions can be found. So it's good that the fermentation field is overcrowded – and that cannabinoid plant extraction is also progressing, Bryant explained. Competition will cut prices and increase availability, she said. "We need all the different sources."
Will consumers care?
Far north of Demetrix’s base in Berkeley, CA, the Canadian company Hyasynth is on the verge of fully producing fermented cannabinoids, said Kevin Chen, CEO of Hyasynth.
Hyasynth also mails DNA sequences, inserts them into yeast genomes, and extracts the desired compounds from the slurry to produce medical grade cannabinoids for sale to pharmaceutical companies.
"It's the modern way," said Chen, who praised the same virtues of fermentation versus agriculture as Demetrix: scaling, consistency, speed, and especially specificity. "We have full control over which cannabinoid we produce and which we don't."
Fermentation is a process that takes five days instead of the three months it would take to plant and grow marijuana to use it for enzyme extraction, he said. Agriculture can be difficult. Once you've determined your specific splicing method, fermentation is easy.
Technical cannabinoids may be superior for pharmaceutical purposes, but not everyone will want cannabis to be grown in tanks or tubes, Chen concedes.
"We are not too concerned about people rejecting our product," Chen said. "We use yeast to make things, but yeast is not what we sell."
From the standpoint of personal preference, not all cannabinoids are the same. Some consumers may prefer a holistic product for the whole plant. Some may only be interested in results.
"Does people care that it comes from another place? Absolutely, ”said Chen. However, different methods of cannabinoid production are suitable for different purposes, and fermentation appears to be winning in a competition for pharmaceutical ingredients. "It's different – it's better in many ways."
Celia Gorman is a science journalist and video editor from New York. She holds a master's degree in digital journalism from the CUNY Graduate School of Journalism and previously worked as an associate editor at the technology magazine IEEE Spectrum, where she developed and managed an award-winning video department.