Plant Chemistry: A Concerted Chemical Process

Plant Chemistry: A Concerted Chemical Process

July 05, 2018

Plant Chemistry

By: Jared Jacob, R&D Formulation Chemist

 

It’s known that a plant produces therapeutically valuable chemicals in its battle for survival, but how does this occur? A plant’s existence is rooted in its ability to combine light, water, soil nutrients, benefits from symbiotic bacteria, and CO2 to create essential components for life: plant primary metabolites. These primary metabolites constitute an array of enzymes, hormones, and chemical building blocks. In its struggle for survival, the plant then uses these chemicals to produce an auxiliary line of compounds: plant secondary metabolites (PSM). While these aren’t essential for existence, they are useful in protection against microbes, herbivores, and extreme conditions. As mentioned in an earlier blog, PSMs and their derivatives constitute many of today’s vitamins and nutraceuticals. Today, we will look closely at the biosynthesis of phytocannabinoids.

The creation of these compounds all begin with starting molecules, which undergo one of two enzymatic pathways—MEP Pathway or Mevalonate Pathway—to yield isoprenoid/terpenoid precursors(1). The terpenoids exhibit pluripotency in that they can subsequently be transformed into any terpene-based PSM depending on which enzyme selects them—a process dictated by survival demands.

The MEP Pathway begins with one molecule each of pyruvic acid and G3P (glyceraldehyde-3-phosphate)(1) (Figure 1). The Mevalonate Pathway, however, begins with just two molecules of acetyl-CoA (Figure 1). While both the MEP and Mevalonate Pathways start off with different chemicals and encounter different enzymes along their respective cascades, the pathways both yield terpenoid isomers DMAPP (dimethylallyl pyrophosphate) and IPP (isopentyl pyrophosphate). IPP and DMAPP can then begin polymerizing with each other, namely via the alkenyl double bonds, to form longer chain terpenoids, such as GPP (geranyl pyrophosphate).

 

MEP and Mevalonate Pathways

Figure 1. MEP and Mevalonate Pathways. George et. Al (2015)

 

GPP is a precursor to many vitamins, antioxidants, terpenes, and plant hormones. It also provides the isoprene chain for the synthesis of cannabinoid CBGA (cannabigerolic acid). In this particular instance a product of the terpenoid pathway meets an intermediate of the polyketide pathway (Figure 2) to create an entire class of compounds beneficial for the cannabis plant’s existence(2).

 

Polyketide Pathway and Eventual CBGA Synthesis

Figure 2. Polyketide Pathway and Eventual CBGA Synthesis. Stout et. Al (2012)(3)

 

It’s quite an elegant concert of chemical reactions which come together to create the primary phytocannabinoid CBGA (cannabigerolic acid).

Environmental conditions and plant maturation then dictate the fate of CBGA. CBGA can be transformed into CBDA (cannabidiolic acid) by CBDA synthase or Δ9-THCA (delta-9-tetrahydrocannabinolic acid) by THCA synthase. In planta, these phytocannabinoids exist in their [carboxylic] acid form but can be decarboxylated upon heating or further processing(3).

This is just one fruit of the isoprenoid/terpenoid pathway; it can also spawn fragrance terpenes, heme, retinol-based vitamins, sterol-based vitamins, and other plant hormones.

 

(1) George, K. W., Alonso-Gutierrez, J., Keasling, J. D., & Lee, T. S. (2015). Isoprenoid Drugs, Biofuels, and Chemicals—Artemisinin, Farnesene, and Beyond. Biotechnology of Isoprenoids Advances in Biochemical Engineering/Biotechnology, 469-469. doi:10.1007/10_2015_310

(2) Gagne, S. J., Stout, J. M., Liu, E., Boubakir, Z., Clark, S. M., & Page, J. E. (2012, July 31). Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides. Retrieved from http://www.pnas.org/content/109/31/12811.long

(3) Stout, J. M., Boubakir, Z., Ambrose, S. J., Purves, R. W., & Page, J. E. (2012). The hexanoyl-CoA precursor for cannabinoid biosynthesis is formed by an acyl-activating enzyme in Cannabis sativa trichomes. The Plant Journal, 353-365. doi:10.1111/j.1365-313x.2012.04949.x