Cannabis Enzymes

Cannabis, commonly known as marijuana, is a psychoactive drug containing compounds like THC and CBD, and is used for recreational purposes, medicine and industrial purposes like hemp. Cannabis as a plant produces multiple secondary metabolites. Cannabinoids like THC, CBD, and CBC interact with the body’s endocannabinoid system, which influences mood, pain, appetite and memory as well as a slew of other effects. Terpenes are aromatic compounds found abundantly in cannabis. They have potential therapeutic effects from interacting with cannabinoids. Flavonoids are produced by many plants to provide color and aroma to them. Additionally, they protect against UV radiation and are concentrated in leaves, seeds, and flowers. They induce the same synergizing effect with cannabinoids that terpenes do. These compounds are produced by cannabis using enzyme-driven biosynthetic pathways. These are a chain of biocatalytic steps that are highly selective and end up converting common compounds into complex, valuable molecules. These can range from pharmaceuticals and natural products to psychoactive drugs. Three things control the type of bioactive compounds a plant produces: precursor-building enzymes, cannabinoid synthases, and gene regulation.

Cannabinoid biosynthesis begins with precursor-building enzymes. These are found primarily in the polyketide and isoprenoid pathways. Polyketide chains are created and formed from simple metabolic units by olivetol synthase. Olivetolic acid is produced by proper ring formation in these pathways which is induced by olivetolic acid cyclase. This acid then combines with the central branching molecule in cannabinoid synthesis and geranyl diphosphate to form cannabigerolic acid. Through oxidative cyclization reactions, cannabigerolic acid is converted into distinct cannabinoid acids by cannabinoid synthase enzymes, each being named after the acid they produce. Small structural changes in each of the enzymes determine what cannabinoid they produce. This process occurs similarly for terpenes, producing terpenes that contribute to aroma, pigmentation, and ecological function.

Biosynthetic enzyme activity is controlled by gene expression which varies based on plant species, tissues, and developmental stage of the plant. High expression occurs in flowers and glandular trichomes where bioactive compounds accumulate. Chemical diversity in cannabis plants is increased by enzyme variants which comes from genetic variation and alternative RNA processing. Alternative RNA processing is what determines enzyme specificity and regulation which allows genetically related plants to produce different amounts of and types of enzymes and chemical profiles. These insights contribute to our  understanding of plants’ secondary metabolism, natural product biosynthesis, and biotechnology applications such as engineered production of bioactive compounds. 

References:

Taura, Futoshi, et al. “Cannabidiolic-Acid Synthase, the Chemotype-Determining Enzyme in the Fiber-Type Cannabis Sativa.” Science Direct, 26 June 2007, www.sciencedirect.com/science/article/pii/S0014579307005728. 

Jin, Dan, et al. “Secondary Metabolites Profiled in Cannabis Inflorescences, Leaves, Stem Barks, and Roots for Medicinal Purposes.” Nature News, Nature Publishing Group, 24 Feb. 2020, www.nature.com/articles/s41598-020-60172-6. 

Thomas, Fabian, et al. “Springer.” Springer Nature Link, 12 Oct. 2020, link.springer.com/content/pdf/10.1007/s00253-020-10798-3.pdf. 

Hu, Jinyuan. “Transcriptomic Analysis of Wild Cannabis Sativa: Insights into Tissue- and Stage-Specific Expression and Secondary Metabolic Regulation.” Springer Nature Link, 26 May 2025, link.springer.com/article/10.1186/s12864-025-11697-5. 

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