The Biosynthesis of Cannabinoids
Posted 6th May 2020 by Joshua Sewell
We recently spoke to Jeremy Friedberg, CSO of LAVVAN, a company pioneering the biosynthesis of cannabinoids. The conversation was recorded as a podcast, which can be found here.
What are the major advantages that biosynthesis of cannabinoids has over traditional cultivation?
To really understand why biosynthesis is important, it is helpful to go back to the five years I spent in the chemistry industry before LAVVAN.
At that time in Canada, a brand new federal regulatory system was coming into place. There was a fundamental shift in the notion of quality, and of what cannabis and cannabis-derived products meant.
Before these federal frameworks, that notion of quality was around Cannabinoid levels, taste, and smell – all very qualitative characteristics. But once federal regulations came into place, we had to start treating the plant like any other crop. We were no longer look at these qualitative metrics. Instead, we were looking at yield, Cannabinoids, yeast and mould levels, microbials, and the absence of any pesticides. This became a very difficult proposition for the cultivation of the plant.
We spent a long time perfecting cultivation to solve these problems. However, as companies grew, we started speaking to a lot of the large suppliers of Cannabinoid infused products and large CBG companies who would become large future buyers: aside from quality, the most important characteristic they needed from Cannabinoids was consistent supply.
With traditional cultivation, it was really difficult (if not impossible) to ensure the level of consistency and purity that those industries required. This is primarily why Biosynthesis is coming to the forefront as it is today. It is solving so many of the problems that exist in the cultivation of the plant.
What are the major challenges currently associated with biosynthesis of cannabinoids?
There are two major components to this process.
Firstly, a process we call cellular agriculture. This involves the engineering of a microorganism to produce Cannabinoids. Secondly, there is the scale-up manufacturing of those Cannabinoids, generally through a fermentation-based process.
The first major hurdle is getting an organism like yeast, E. Coli or algae (in our case we’re using yeast as a foundation) to produce Cannabinoids – which they normally don’t do. Bringing the Biosynthetic pathway from the cannabis plant into this organism was an initial challenge, which is solved and published in the literature.
Once it is in the organism, we then have to work with the organism to get it to produce Cannabinoids in the way we want. It is really about controlling the materials to produce at the levels that make it economically viable. This is something that “LAVVAN” has achieved as well, which is not an insignificant hurdle to overcome.
Once you have those two challenges met, you now have to move into manufacturing and scaling up: from a bench-top fermentation experiment to hundreds of thousands of litres of fermentation vessels. This is an enormously difficult proposition, and where there are significant challenges to be met.
We have overcome them and will be in manufacturing in the later part of 2020. These are significant challenges in the industry and all of these problems need to be solved.
However, this not to be underestimated from just a technical perspective. From an economic perspective, this is also really important. CBD is very popular as a Cannabinoid and is being widely used. As the market grows, the relative cost of CBD is going to drop. Unless you can scale up and reduce costs significantly, you are never going to be able to move with the market trends as the value of CBD changes over time.
What are the other exciting Cannabinoids being discovered besides CBD and THC?
From the literature, there are well over 150 different Cannabinoids that have been identified from the plant. Some even report 180-200.
Most of them are observed in extremely trace amounts and the big ones that are seen are obviously CBD and THC. There are some other ones where there is a direct biosynthetic pathway to produce them (like CBC), and there are others that are produced after the fact: modified Cannabinoids like CBN, CBL and a variety of others.
The literature is only just starting to catch up with where we are in the market today. There is a tremendous amount of interest in what is referred to as the ‘minor’ Cannabinoids, which are found in very small concentrations. We are going to see interest and utility grow around these Cannabinoids. Most recently there is THC and CBDP, which was discovered to have a very potent effect on the CB1 and CB2 receptors.
All of these are going to become of more significant interest over time. It will require research to show that they are safe and exactly what they do to the body, i.e. to really understand what their utility would be in the future.
What about terpenes?
Terpenes are interesting: in the literature, there is quite a bit of information showing that terpenes themselves have potential therapeutic effects or when you consume the plant material, are affecting the way Cannabinoids are absorbed into the body.
What I think is very interesting is that there is something different about the whole plant extract in its efficacy on the body versus isolate. I don’t think terpenes are going to go away in a meaningful way. People are still going to consume plant materials and people are still going to want to consume the whole plant extract.
The difference is that terpenes are a molecule just like Cannabinoids. Biosynthesis is a platform that allows us to produce molecules, so we can produce terpenes that aren’t available in any other source.
But when it comes to the approach that Biosynthesis is taking in this space is not about trying to get the organism to produce a whole plant extract. It’s getting the organism to produce low cost, high quality, very consistent, individual molecules and then you can do whatever you want with them. You can recreate the formulation that you find in a plant and if that includes terpenes, you can do that.
What is your outlook for the future of synthesized Cannabinoids? Do you think this is something that would replace traditional cultivation?
I don’t think it would replace it. There would always be a market for “dry flower” material and “fresh flower” material.
The question will be “what is that market?” What the trends are saying right now is that the market would always exist, but it is much smaller than it would be in the future.
What the market is really pointing to is a significant amount of Cannabinoid raw material to be put into all kind of products.
Estimates are that by 2025 the market will produce 250 thousand kilograms of purified Cannabinoids, just to meet that market demand on an annual basis. Producing all that cost-effectively, and with a level of safety and purity, just can’t be done in the plant.
The cultivation of the plant for that utility will drop away very, very quickly over the next five years.
Platforms like Biosynthesis and cellular agriculture are going to become the forefront in Cannabinoid production, to meet that infused market demand because they can produce consistently and meet that market demand.
Jeremy Friedberg is CSO at LAVVAN.
The 5th Medicinal Chemistry & Protein Degradation Summit will feature a one-day symposium on Cannabinoid Drug Discovery, exploring the latest drug discovery developments in this new class of regulated therapeutics. Find out more here.
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Apart from the enzymes responsible for cannabinoid precursor biosynthesis, only three enzymes are known to be involved in the biosynthesis of cannabinoids.