Researchers identify high-efficiency hacks used by cannabis cells to make cannabinoids
For the first time, plant biologists have defined the high-efficiency “hacks” that cannabis cells use to make cannabinoids (THC/CBD). Although many biotech companies are currently trying to produce THC/CBD outside of the plant in yeast or cell cultures, it is largely unknown how the plant does this naturally.
“This really helps us understand how cannabis trichome cells can pump out massive amounts of tetrahydrocannabinol (THC) and terpenes – compounds that are toxic to plant cells in high amounts – without poisoning themselves,” says Dr. Sam Livingston, a University of British Columbia botanist who led the research.
“This new model may inform synthetic biology approaches to cannabinoid production in yeast, which is commonly used in biotechnology. Without these ‘tricks’, they will never achieve efficient production.”
For centuries, humans have cultivated cannabis for the pharmacological properties resulting from the consumption of its specialized metabolites, primarily CBD and terpenoids. Today, production in the $20 billion global cannabis market relies heavily on the biological activity of tiny clumps of cells, called glandular trichomes, found primarily on the flowers of the plant.
The study, published today in Current biologyreveals the microenvironments in which THC is produced and transported in cannabis trichomes, and sheds light on several critical points in the pathway of THC or CBD manufacture in the cell.
Dr. Livingston and co-author Dr. Lacey Samuels used rapid freezing of cannabis glandular trichomes to immobilize plant cellular structures and metabolites in situ. This allowed them to study the glandular trichomes of cannabis using electron microscopes which revealed the cellular structure at the nano level, showing that the metabolically active cells of cannabis form a “supercell” which acts as a tiny metabolic biofactory.
So far, synthetic biology approaches have focused on optimizing the enzymes responsible for making THC/CBD, such as building a factory with the most efficient machinery to make as many products as possible. However, these approaches have not developed an efficient way to move intermediate substances from one enzyme to another, or from inside the cell to outside the cell where the end products can be collected. This research helps define the subcellular “shipping routes” that cannabis uses to create an efficient pipeline from raw materials to finished products without accumulating toxins or waste.
“For more than 40 years, everything we thought about cannabis cells was inaccurate because it was based on dated electron microscopy,” says UBC plant cell biologist Dr. Samuels. “This work defines how cannabis cells make their product. It is a paradigm shift after many years, producing a new vision of cannabinoid production. This work has been difficult, in part due to the legal prohibition and also due to the fact that no protocol for the genetic transformation of cannabis has been published.”