Biosynthesis of Cannabinoids Essay

Cannabinoids are a group of tarpenopholics usually associated with Cannabis sativa

commonly known as marijuana where they are mostly found in their glandular trichomes (Fellermeier, et al.). Many people take cannabinoids sorely as marijuana component which is not the case, they are found in plants as well as animals playing different biological roles. Just as other biochemical compounds found in the body, cannabinoids are biosynthetically assembled in the cell with different precursor molecules and with the aid of enzymes. One of the commonly used methods for tracking biosynthesis pathways is by the use of labeled molecular elements like carbon-14 or carbon-13. Labeled carbon-13 experiments have been successfully used to demonstrate cannabinoids bio-synthetic pathway.

Cannabinoids Bio-synthetic Pathway

            There are two major pathways explaining biosynthesis of cannabinoids metacyclic pathways and olivetol biosynthesis pathways. Cannabinoids biosynthesis rely on prenylated polyketides and which are derivatives of fatty acids and isoprenoid precursors. Biosynthesis begins by conversion of hexanoate to hexanoyl-CoA. After this step, two proposed pathways are possible depending on the next substrate. 

In the metacyclic pathway, hexanoyl-CoA may be converted into 3,5-dioxodecanoyl-CoA, then to 3,5,7-trioxododecanoyl-CoA which is finally converted to olivetorate which is later changed to canabigerolate in the metacyclic pathway. The canabigerolate produced in the metacyclic pathways is finally converted into tetrahydrocannabinolate, cannabidiolate, cinnabichromerate before they are converted into tetrahydrocannabinol, cannabidiol, and cinnabichromene respectively which are cannabinoids.

In olivetol biosynthesis type III polyketide synthase catalyzes the formation of Olivotelic acid by condensing Hexanoyl-CoA with three molecules of manonyl-CoA. The same enzyme type III polyketide synthase first facilitate the formation of by-products like Olivetol, pentyl diacetic acid lactone and hexanoyl triacetic acid lactone which are used in other biosynthetic pathways. The produced Olivotelic acid is then geranylated, thus changed to cannabigerolic acid. Cannabegerolic acid is then converted to major cannabinoids by the action of oxidocyclase enzymes to form the major types of cannabinoid acids. The two major types of cannabinoids produced by the help of oxidocyclase enzymes are tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). The final step to biosynthesis of cannabinoids is non-enzymatic decarboxylation to their neutral forms rather than their acidic forms which are more likely to be prone to further biosynthetic changes. Tetrahydrocannabinolic acid becomes tetrahydrocannabinol while cannabidiolic acid becomes cannabidiol. Even though, the exact enzymes and their functioning has not yet been discovered with attempts from scientists from many parts of the world trying to identify the polyketide synthase (PKS) groups of enzymes without success using cannabis as a model (Stout).

            Major enzymes responsible for the formation of cannabinoids in Cannabis sativa

have been identified in other living cells in different living organisms like Escherichia coli as well as in animals cells acting as proof to cannabinoid biosynthetic pathways in other organisms other than Marijuana (Fellermeier, et al.). Even though, cannabinoids bio-synthetic pathways have not been widely studied, therefore, with different biosynthetic pathways being suggested and declined ("MetaCyc Cannabinoid Biosynthesis"). Polyketide synthase enzymes identity has also been suggested but not satisfactory.

Works Cited

Fellermeier, Monika, et al. "Biosynthesis of cannabinoids Incorporation experiments with 13C-labeled glucoses." European Journal of Biochemistry, vol. 268, no. 6, 2001, pp. 1596-1604.

"MetaCyc Cannabinoid Biosynthesis." BioCyc Pathway/Genome Database Collection, biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-5140.

Stout, Jake M. "Identification of Olivetolic Acid Cyclase from Cannabis Sativa Reveals a Unique Catalytic Route to Plant Polyketides." ResearchGate, www.researchgate.net/publication/229157196_Identification_of_olivetolic_acid_cyclase_from_Cannabis_sativa_reveals_a_unique_catalytic_route_to_plant_polyketides.