U of S researchers discover cannabis “pharma factory”

U of S researchers have discovered the chemical pathway that Cannabis sativa uses to create bioactive compounds called cannabinoids, paving the way for the development of marijuana varieties to produce pharmaceuticals or cannabinoid-free industrial hemp. The research was published online in the July 16 early edition of the Proceedings of the National Academy of Sciences (PNAS).

U of S adjunct professor of biology Jon Page explains that the pathway is an unusual one, involving a specialized version of one enzyme, called hexanoyl-CoA synthetase, and another enzyme, called olivetolic acid cyclase (OAC), that has never before been seen in plants.

“What cannabis has done is take a rare fatty acid with a simple, six-carbon chain and use it as a building block to make something chemically complex and pharmacologically active,” Page says.

Cannabis has been cultivated for thousands of years for food, fibre, medicine and as a psychoactive drug. Cannabinoids such as delta-9-tetrahydrocannabinol, or THC, are produced on the flowers of the female plant in tiny hair-like structures called trichomes, the plant’s own “chemical factories.” The researchers used genomic analysis of isolated trichome cells to produce a catalog of the genes involved in cannabinoid production.

Page led the research with PhD student Steve Gagne, who discovered OAC, and postdoctoral researcher Jake Stout, who discovered hexanoyl-CoA synthetase (reported earlier this year in The Plant Journal). Page and his colleagues have already used the new enzymes to coax yeast to produce olivetolic acid, a key metabolic intermediate on the biochemical pathway that leads to cannabinoids.

“Now that we know the pathway, we could develop ways to produce cannabinoids with yeast or other microorganisms, which could be a valuable alternative to chemical synthesis for producing cannabinoids for the pharmaceutical industry,” Page says.

Funding for this research was provided by the Natural Sciences and Engineering Research Council (NSERC), the Genome Canada PhytoMetaSyn project, Genome Prairie, Saskatchewan Ministry of Agriculture and the National Research Council.