Researchers produce cannabinoids by using yeast

Environment and sustainability 13. may 2019 3 min Professor Jay D. Keasling Written by Kristian Sjøgren

The market for cannabis has taken off in recent years, and it will definitely grow in the future. Researchers have finally discovered how they can synthesize the relevant cannabinoid compounds in cannabis by using yeast, opening up new pharmaceutical applications.

The cannabis plant contains more than 100 cannabinoids; the two most commonly known are tetrahydrocannabinol (THC) and cannabidiol (CBD).

More and more countries are now legalizing cannabis products. In Denmark, certain cannabinoid formulations have also been approved for use, which enables people to obtain prescriptions for, among other things, tea with cannabis or CBD oil.

Cannabinoids have both pharmaceutical and relaxing effects on humans. People with epilepsy or multiple sclerosis, for example, often benefit from treatments with cannabis products, and skin care products and coffee containing cannabinoids are now available. Breweries are also starting to examine the possibility of making cannabinoid beer, and soft drink manufacturers want to make sports drinks containing cannabinoids.

The need for controlled synthesis of large amounts of cannabinoids is therefore rapidly growing, and researchers have now succeeded in getting yeast to produce them for the first time. This opens up even more potential applications of cannabis.

“Cannabinoids are both expensive to produce synthetically and bad for the environment, and producing them through traditional cannabis cultivation is still illegal in many countries. A different production method is therefore required, and yeast is an obvious candidate. We can now produce cannabinoids through an ordinary fermentation process, similar to making beer,” explains the researcher behind the cannabinoid yeast, Jay Keasling, Professor, Keasling Lab, University of California, Berkeley and Scientific Director, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark.

The spectacular results were recently published in Nature.

Cannabinoids are already being used pharmaceutically

THC is the most psychoactive substance in the cannabis plant and is currently used pharmaceutically for treating such ailments as nausea and vomiting in connection with chemotherapy and anorexia and to counteract weight loss among people living with HIV.

CBD is used to treat epilepsy and other disorders of the nervous system.

Researchers know little about the properties of the many other cannabinoids in cannabis. However, they need to isolate them individually to carry out experiments.

The current price of synthesizing cannabinoids is USD 40,000–70,000 per kg. The price for making them with Jay Keasling’s yeast will be USD 400.

Producing cannabinoids using yeast also costs only 10% of the cost of growing cannabis in a greenhouse, and price is not the only advantage.

“Cultivating cannabis is both expensive and bad for the environment. Growing cannabis requires an estimated 3% of all electricity used in California, and the production process also uses large amounts of water. In addition, producing cannabis is very wasteful because only the plant shoots are used. Production using yeast creates none of these problems,” says Jay Keasling.

Synthesizing unnatural cannabinoids with yeast

In addition to producing the pure cannabinoids for a fraction of the price, the newly developed cannabinoid yeast also has a third advantage: the researchers can create completely new forms of unnatural cannabinoid analogues.

Adding various fatty acids to the yeast produces various cannabinoids the natural plant cannot produce. According to Jay Keasling, some of these may therefore be developed into pharmaceutical breakthroughs.

Among other things, various chemical changes in the cannabinoids might make them more potent, provide them with other effects or enable them to bind to various types of medicine, thereby creating new types of combination treatment.

“The yeast is a little imprecise in producing the various cannabinoids, and this means that it can produce some cannabinoid analogues that the plant cannot. This is very beneficial for discovering cannabinoids with either new or more potent properties,” says Jay Keasling.

Jay Keasling and the University of California, Berkeley have patented the cannabinoid yeast and launched Demetrix, a company that aims to develop new types of medicine based on the opportunities opened up by cannabinoid yeast.

“We can already synthesize exactly what people need. Right now, we are focusing on the natural and commonest types of cannabinoids, but later on, we plan to move to the rare and unnatural types. We will definitely collaborate with the pharmaceutical industry and the University in testing various cannabinoids to treat various diseases,” says Jay Keasling.

Splicing genes from other organisms into yeast

The researchers took five genes from the cannabis plant and from other organisms and spliced them into the yeast cells.

The genes encode various steps in the process that eventually results in the production of cannabinoids.

The researchers selected some genes from other organisms in places where the genes are more efficient than the cannabis genes in making the basic molecules that later become cannabinoids. They then used specialized genes from the cannabis plant to make the final cannabinoids.

“The genes encode various enzymes, and we chose the most efficient ones available,” explains Jay Keasling.

Researchers racing to develop cannabinoid yeast

Jay Keasling’s research team was not the only one striving to get yeast to produce cannabinoids.

The market for cannabis products is growing tremendously, so every patent is a potential gold mine.

The race between the various research groups trying to do what Jay Keasling ended up doing first was therefore intense.

Many of the other researchers got stuck when they tried to find an enzyme that creates the parent molecule from which all cannabinoids are formed.

Canadian scientists had already patented the discovery of an enzyme they believed was responsible for the process.

However, no matter how hard Jay Keasling and his research team tried to splice the gene for that enzyme into their yeast, they could not make it work. This made them go back to the cannabis plant and search again.

They found another gene in the plant, spliced it into their yeast, and it began to produce huge quantities of cannabinoids.

“This problem was so great that it became a barrier for many of the other research groups, and we ended up winning the race,” says Jay Keasling.

Complete biosynthesis of cannabinoids and their unnatural analogues in yeast” has been published in Nature. Jay Keasling is Professor of Chemical Engineering and Bioengineering and Principal Investigator, Keasling Lab, University of California, Berkeley and Lawrence Berkeley National Laboratory and Scientific Director, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark.

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