Science

Producing Cannabinoids from Non-Cannabis Sources

Loren DeVito, PhD
Written by Loren DeVito, PhD

Potential benefits, possible limitations, and  current technology

Editor’s Note: This article, like several others we’ve written, discusses alternative methods for cannabinoid production. The fact that we are covering this does not mean that we support these techniques. Rather, being an unbiased cannabis science publication and educational platform, we feel it’s our duty to report current cannabis science and technology to our readers, whether it’s controversial or well-accepted.

Long gone are the days when cannabinoids were produced exclusively from the cannabis plant. Following advancements in both genetics and technology, several companies have now developed proprietary platforms designed to produce cannabinoids from non-cannabis sources.

Cannabis consumers may have some questions on the new techniques being used to produce the products they (one day) may consume—especially if they happen to be a long-time consumer who is more familiar and comfortable with consuming these molecules as produced by the plant.

For starters, it’s important to discuss why expressing and producing these compounds from a non-cannabis source is beneficial. It’s certainly no secret that demands for cannabis concentrates have skyrocketed—not to mention that sweeping legalization has created a new market of novice users or those who are not as familiar with concentrates.

The trouble with, or rather limitations of, extracting cannabinoids from the cannabis plant center on scalability. It takes a large quantity of cannabis plants to produce a small amount of concentrate—and growing those plants takes time, money, and land. Another benefit of going around the plant is the elimination of pesky pesticides that can sneak into the final product.1

Additionally, medical cannabis patients often need very high doses of cannabis to treat certain conditions. For example, While this medication is FDA-approved and therefore may be covered by insurance, patients accessing medical cannabis from dispensaries must (currently) pay out of pocket. Of course, there’s no guarantee that products from non-cannabis sources will be less expensive, but the cost to produce them should certainly be lower.

So, how are these proprietary platforms designed and what sources are being used?

Studies have reported the successful production of cannabinoids from different non-cannabis sources, including yeast (Saccharomyces cerevisiae, Pichia (Komagataella) pastoris, and potentially others) and bacteria (E. coli).1-3 Using microorganisms not only allows for faster production but also the potential for improved compounds by altering pharmacokinetic properties.1 But, to do this, the metabolic pathways of the model organisms used must first be transformed to produce the compounds of interest.

Within the cannabis plant, biosynthesis begins with the conversion of hexanoic acid to its form attached to coenzyme A. From there, olivetolic acid is created in part by type III polyketide synthase (PKS). Then, PKS olivetol synthase produces olivetol.1 Still with me in this alphabet soup?

Cannabigerolic acid synthase, or CBGAS, orchestrates the process by which CBGA is born. CBGA is often described as the “mother of all cannabinoids,” and for good reason. It’s the precursor to tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), and cannabichromenic acid (CBCA) that together produce the more familiar cannabinoids, such as CBG, THC, CBD, and CBC.

Now, back to microorganisms.

To get yeast or bacteria to start making cannabinoids, researchers have genetically “hacked” their metabolic pathways to create a more streamlined approach toward production. In one study, for example, researchers inserted expression cassettes into a yeast strain to boost the production of olivetolic acid, which, in conjunction with additional genetic alterations, kickstarted the cannabinoid production process.2

Librede is one company taking advantage of producing cannabinoids from yeast. In fact, their web site emphasizes the environmental benefit of this approach, citing the burden of traditional cannabinoid production that requires large quantities of water and use of fertilizers and pesticides. And Renew, another cannabis company, is developing technology from microalgae, with the goal of creating a biosynthetic treatment for traumatic brain injuries.

While these all represent incredibly promising technologies, time will tell whether products created from cannabinoids produced outside of the cannabis plant will hold the same, or improved, therapeutic properties, and if alternative methods can produce higher quantities of cannabinoids not possible through traditional techniques.

Whether for environmental and therapeutic benefits or cost reductions, it seems as though these methods will continue to be refined as more companies enter the industry. Devoted to the cannabis plant alone? Rest assured, thousands of years of use largely ensures that the famous plant is not going anywhere anytime soon.

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References

  1. Carvalho, A., et al. “Designing Microorganisms For Heterologous Biosynthesis of Cannabinoids.” FEMS Yeast Res. vol.17, no.4, 2017, pp. 1-11. (impact factor: 2.458; cited by: 9).
  2. Luo, X., et al., “Complete Biosynthesis of Cannabinoids And Their Unnatural Analogues in Yeast.” Nature. vol.567, no.7746, 2019, pp. 123-126. (impact factor: 41.577; cited by: 7)
  3. Zirpel, B., et al., “Production of Δ9-tetrahydrocannabinolic Acid from Cannabigerolic Acid by Whole Cells of Pichia (Komagataella) pastoris Expressing Δ9-tetrahydrocannabinolic Acid Synthase from Cannabis sativa ” Biotechnology Letters, vol.37, no.9, 2015, pp. 1869-1875. (impact factor: 1.155; cited by: 23)

About the author

Loren DeVito, PhD

Loren DeVito, PhD

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