Researchers at Wageningen University & Research have recreated enzymes from cannabis ancestors millions of years old, revealing how the plant evolved to produce compounds like THC, CBD, and CBC. These ancient enzymes, more flexible than modern versions, show potential for easier biotechnological production of cannabinoids for medical use. The findings, published in Plant Biotechnology Journal, could lead to new medicinal cannabis varieties.
Cannabis plants today produce key cannabinoids—THC, CBD, and CBC—using specialized enzymes, each dedicated to a single compound. A study from Wageningen University & Research demonstrates that this precision emerged through evolution. Early ancestors of cannabis possessed more versatile enzymes capable of generating multiple cannabinoids simultaneously.
To trace this development, the team employed ancestral sequence reconstruction, analyzing DNA from modern plants to predict and rebuild enzymes active millions of years ago. These resurrected enzymes were then synthesized in the lab and tested, providing the first experimental evidence of how cannabinoid biosynthesis originated in a recent cannabis ancestor and refined over time through gene duplications.
The research uncovered practical advantages: the ancient enzymes proved more robust and easier to express in microorganisms like yeast compared to contemporary ones. This could streamline biotechnological manufacturing of cannabinoids, which are increasingly produced outside plants for medical applications.
"What once seemed evolutionarily 'unfinished' turns out to be highly useful," noted lead researcher Robin van Velzen, who collaborated with Cloé Villard. "These ancestral enzymes are more robust and flexible than their descendants, which makes them very attractive starting points for new applications in biotechnology and pharmaceutical research."
Particularly promising is an ancient enzyme that specifically produces CBC, known for anti-inflammatory and analgesic effects. No current cannabis variety naturally yields high CBC levels, so integrating this enzyme could create innovative medicinal strains. The study, detailed in Plant Biotechnology Journal (DOI: 10.1111/pbi.70475), bridges evolutionary biology with potential health benefits.
