The Budding Promise of Cannabinoid Biosynthesis

By: John Selwanes

Edited by: Guy Beretich

Keywords: cannabinoids, cannabis, biosynthesis

In the last month, I have encountered an increasing number of issued cannabinoid biosynthesis patents and published patent applications filed by biotechnology, pharmaceutical, and therapeutics companies. Unless you are familiar with life sciences, you may not fully understand the process of biosynthesis and its market potential in many industries. So what does biosynthesis entail, you might ask?

Without getting too much into bio-engineering, a microorganism’s genetics are altered so that it is able to turn a particular molecule into another as part of its metabolic processes. Preferably, yeast, E. coli, or agrobacterium are used, since the genetic vectors, the genes that are “transplanted” into the organism, are well-developed, as well as the methods of transforming the microorganism to contain the altered genetic makeup. For example, one could transform a yeast cell to express the enzyme THCA synthase so that the yeast cell can transform CBGA into THCA, the precursor of THC. Synthases are enzymes that link two molecules together to create another molecule. The cannabinoids of interest are then purified. But this is limited in that CBGA is required to be produced beforehand and in good abundance, such as from a cannabis plant. But could there be a way to synthesize cannabinoids without a cannabinoid precursor molecule at the start of the process?

Enter CB Therapeutics. CB Therapeutics has been unlocking the potential of microorganisms since 2015, bio-engineering novel strains of yeast capable of producing high-value molecules. CB’s first assigned patent application for the biosynthesis of CBGA and CBGVA using yeast was filed in September of 2017 for US patent publication No. 20180155748, now issued patent No. 10,435,727. CBGA and CBGVA are the parent molecules to dozens of therapeutic cannabinoids, giving them immense worth. Patent ‘5,727 is the first patent to Magic Number’s knowledge that discloses the complete biosynthesis of cannabinoids from simple sugars. CB Therapeutics’ process begins with transforming yeast cells to produce the required synthases needed to synthesize CBGA and CBGVA starting from a glucose molecule. Additional enzymes needed to catalyze the production of the cannabinoids are added to the yeast as well. Synthesis of cannabinoids in this manner boasts many advantages to growing cannabis plants for cannabinoid extraction.

Notably, the cost of producing cannabinoids from a microorganism rather than from a cannabis plant is highly competitive, not to mention vastly quicker. For example, a kilogram of finished cannabis products can cost as much as $2,500 in electricity to grow the traditional way according to the National Conference of State Legislators (NCSL). Put simply by the NCSL, a four-plant lighting module can use as much energy as 29 refrigerators. In contrast, a yeast culture can begin producing cannabinoids as soon as 12 hours into growth and can be ready to filter in as little as a day. Biosynthesis can be tailored so that only one compound of interest is synthesized, reducing the risk of contamination and reducing the cost of purification. There is no need for pesticides, which reduces the costs for post-production processing and analysis, as well. Finally, culturing yeast does not consume large amounts of space, attracting many industries that require cannabinoids for their products.

Industries that will benefit considerably from biosynthesized cannabinoids include: Pharmaceutical, Food and Beverage, and Health and Cosmetics. What they all have in common is that they don’t sell finished cannabis products, but rather goods containing cannabinoids, so it is likely that they will choose the most economic option. Further, these industries cannot afford to have an order for CBD concentrate cancelled due to a harvest testing hot for THC, which makes biosynthesis all the more attractive.

Cannabinoid biosynthesis needs to be scaled-up to meet market demands as well as achieve economies of scale. And CB Therapeutics claims to be near commercial-level production: CB Therapeutics has successfully scaled the process to 400 liter bioreactors. But CB Therapeutics is not alone in the cannabinoid biosynthesis space. To Magic Number’s knowledge, there are 20 companies and one independent inventor involved in cannabinoid biosynthesis; however, only four are assigned patents or patent applications disclosing the synthesis of cannabinoids in yeast from sugars. These include Librede, the National Science Foundation, Syntiva Therapeutics, as well as CB Therapeutics.

Interestingly, Librede has begun formulating custom cannabinoid profiles tailored to their customers’ needs as well as novel cannabinoids. A remarkable trait of biosynthesis is its controllability. The ability to determine which cannabinoids will be produced and in what quantities provides great value for the technology. In particular, research of uncommon cannabinoids naturally produced in small amounts can finally be achieved by increasing production through biosynthesis, which, at least partially, explains why we see the NSF in this space.

While cannabinoid biosynthesis is a silver bullet for some, can it actually replace growing cannabis?

In short, no. Just as some of us enjoy beer, cheese, and wine, there are people who enjoy weed, especially as a social experience. Social and complete sensory experiences will outweigh a quick fix.

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