The chemistry of pot

We all know that THC (Δ⁹-Tetrahydrocannabinol) is the main active ingredient of marijuana. However, you may not be aware of the high-tech research going into figuring out how pot plants make THC.

A recent paper published in the Proceedings of the National Academy of Sciences of the United States of America (affectionately known as PNAS) illustrates how some of this research is carried out.

To produce THC, cannabis employs a number of differenet enymes which work in a linear series simplified below:

hexanoyl-CoA + malonylCoA --> OA --> CBGA --> THCA --> THC

Each of the arrows is a different enzyme. A big challenge in understanding how cannabis makes THC (and maybe to be able to make it artificially) is identifying each of the enzymes. As the biochemistry behind this pathway is very complex, this has not been a simple matter.

trichomes on a Cannabis sativa leaf

The lab of Jonathan Page in Saskatchewan figures that the genes encoding these enzymes should be specifically enriched in the THC-rich trichomes, the sticky, furry things on cannabis leaves. They first identified all the genes that are expressed in these trichomes, and then, using their knowledge of enzymology, sought out particular genes that looked like a particular class of enzymes that could potentially take part in the chemistry of the first arrow. They found three candidate genes, and then put each into E.coli to make the proteins. When they added these proteins to hexanoyl-CoA and malonylCoA, the precuursors of OA, they found OA is the mixture. In other words, they identified gene encoding the enzyme for the first arrow. 


When they put this gene in yeast, the yeast started making OA. Just think of the possibilities for beer if they wold add the genes for the arrows...