Terpene Biosynthesis In Vivo

Or, How Terpenes are Made Inside a Cannabis Plant

It all starts with the biochemical capability of plants to undergo photosynthesis. Leaves take up gaseous carbon dioxide (CO2) from the air, and using the complex machinery of the chlorophyll, coupled with the energy provided by photons from the sun (or a high-energy growing lamp), convert CO2 into simple carbohydrates and oxygen gas (O2). Ironically (and luckily for us), oxygen is a byproduct of this reaction, meaning plants don’t use it for themselves, but rather produce it in a symbiotic relationship with the fauna around us, so we all continue to have air to breathe. But, it is the carbohydrates produced concomitantly that we are going to be following today.

The main components worthy of mentioning are the carbohydrates acetyl-coenzyme A (acetyl-CoA) and pyruvate, carbons bound to hydrogen molecules, which go on to form everything from the simple sugars that make fruit taste sweet (fructose and glucose) to the structural fibers that holds the plant matrix together and upright (starch and cellulose) and the lipids that keep the plant insulated and stores its energy for later use.

Once our starting materials have been made, enzymes quickly convert them into reactive intermediaries using energy stored in the abundant phosphate (phosphorus bound to four oxygen atoms) groups present throughout living cells usually coupled to the de-phosphorylation of adenosine triphosphate (ATP, the so-called ‘energy currency’ of the cell).

There are two major pathways for the biosynthesis of these terpene precursors: the mevalonic acid pathway, which uses acetyl-CoA as its starting point and ends in the molecule isopentyl pyrophosphate (IPP) [1], and the methylerythritol phosphate pathway, which uses two intermediates of glycolysis, pyruvate and glyceraldehyde-3-phosphate, to eventually generate both IPP and the structurally-similar dimethylallyl diphosphate (DMAPP). [2] These activated reagents, IPP and DMAPP, are both 5-carbon mono-unsaturated precursors. That means they have one “double-bond”, albeit in different positions.

These precursors are transported and taken up by a myriad of enzymes in the glands of the cannabis leaves that are collectively termed terpene synthases. [3] Each synthase is an enzyme that carries out a particular function in the creation of one particular terpene, and genetically, they are all closely related to one another. In fact, studies have shown that plants can create novel terpene synthases for the generation of new terpenes by only minor alterations of a copy of the terpene synthase gene, accounting for the truly astounding diversity visible in the world of plant terpene morphology. [4] Regardless of where they end, All Roads Lead to Rome, as the saying goes. And in this case, IPP and DMAPP are combined to form the Father of All Terpenoids, geranyl diphosphate (see figure below).

Geranyl diphosphate (or GPP for short) is a unique molecule, in that it has ten carbon atoms and two double-bonds. This makes it ideal for conforming to many resulting combinations of shapes, and the double bonds provide molecular attachment points for additional important elements like oxygen to anchor where needed. It also still has a bound pyrophosphate group (two phosphates attached to each other), making it energetically primed and ready for continued action. It’s ready for more!

In animals, geranyl diphosphate is part of the HMG-CoA (3-hydroxy-3-methyl-glutaryl-coenzyme A) reductase pathway, which provides, among other things, cholesterol and many of the long-distance messenger hormones that our cells use to communicate with each other. In the cannabis plant, GPP is used, in part, to make both cannabinoids and terpenes. [3] It’s the foundation of where everything goes, so any understanding of terpene synthesis in vivo must begin here!


  1. Lange, B.M. and Ahkami, A.Metabolic engineering of plant monoterpenes, sesquiterpenes and diterpenes–current status and future opportunities”. Plant Biotechnol J. 2013; 11(2): 169-96 [Times cited = 133, Journal impact factor = 6.305].
  2. Cunningham, F.X. Jr et al. “Evidence of a role for LytB in the nonmevalonate pathway of isoprenoid biosynthesis”. J Bacteriol. 2000; 182(20): 5841-8 [Times cited = 202, Journal impact factor = 219].
  3. Singh, B. and Sharma, Ram A. “Plant terpenes: defense responses, phylogenetic analysis, regulation and clinical applications”. 3 Biotech. 2015; 5(2): 129–151 [Times cited = 102, Journal impact factor = 1.497].
  4. Booth, Judith K., et al. “Terpene synthases from Cannabis sativa”. PLOS ONE. 2017; 12(3): e0173911 [Times cited = 30, Journal impact factor = 766].

Image Credit: Wikimedia Commons

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