For the first time, plant biologists have defined the highly efficient “hacks” that cannabis cells use to make cannabinoids (THC/CBD). Although many biotech companies are currently trying to engineer THC/CBD out of the plant in yeast or cell cultures, how the plant does this naturally is largely unknown.
“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 botanist at the University of British Columbia who led the research.
“This new model can 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 that result from the consumption of its specialized metabolites, primarily CBD and terpenoids. Today, production within the $20 billion global cannabis market relies heavily on the biological activity of small clusters of cells, called glandular trichomes, found primarily in the plant’s flowers.
The study, published today in Current Biology, reveals the microenvironments in which THC is produced and transported in cannabis trichomes, and illuminates several critical points in the THC or CBD manufacturing pathway within the cell .
Dr. Livingston and co-author Dr. Lacey Samuels used snap-freezing of cannabis glandular trichomes to immobilize the plant’s cellular structures and metabolites in situ. This allowed them to investigate cannabis glandular trichomes using electron microscopes that revealed cellular structure at the nanoscale, showing that metabolically active cannabis cells form a ‘supercell’ that acts as a tiny metabolic biofactory .
Until now, synthetic biology approaches have focused on optimizing the enzymes responsible for making THC/CBD, like building a factory with the most efficient machinery to make as much product as possible. However, these approaches have not developed an efficient way to move intermediates 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 final products without accumulating toxins or waste products.
“For more than 40 years, everything we thought about cannabis cells was inaccurate because it was based on dated electron microscopy,” says Dr. Samuels, a plant cell biologist at UBC. “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 challenging, partly as a result of legal prohibition and also due to the fact that there is no protocol for the production of cannabinoids. the genetic transformation of cannabis has been published.”
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Materials provided by University of British Columbia. Note: Content can be edited for style and length.