Scientists are taking a deeper look at the origins of cannabis chemistry by reconstructing enzymes from ancient plants, offering new insight into how cannabis first developed the ability to produce compounds like THC and CBD.
In a recent study published in Plant Biotechnology Journal, researchers at Wageningen University & Research rebuilt molecular structures that existed millions of years ago, revealing that ancient forms of cannabis enzymes were more flexible and robust than those found in modern plants.
The team behind the research says they have successfully traced the evolution of cannabinoid chemistry and identified molecular tools that could improve the biotechnological production of modern medicinal cannabinoids.
The Origin of Cannabinoids
In modern cannabis plants, specialized enzymes are responsible for making individual cannabinoids like THC or CBD. Each enzyme is highly efficient at producing one specific compound. The new study shows that this precision is a recent development in cannabis evolution, rather than something that existed from the start.
Early ancestors of cannabis used versatile enzymes that could create several cannabinoids at once. These enzymes became more specialized over time as gene duplication occurred. This led to the distinct chemical profiles seen in cannabis plants today.
The research team provided direct evidence for this evolutionary process by reconstructing ancient cannabis enzymes in the lab. Their results show that the pathways for creating specific cannabinoids like THC appeared relatively recently and became more specialized over time through natural selection.
Rebuilding Lost Enzymes
The team relied on ancestral sequence reconstruction to study this evolutionary history. They compared DNA from modern cannabis and related species to determine what cannabinoid-producing enzymes looked like millions of years ago.
The researchers synthesized the predicted enzymes and tested their functions in the lab. Many of the reconstructed enzymes converted precursor molecules into several different cannabinoids, unlike the more specialized modern enzymes.
These experiments enabled the team to directly test evolutionary hypotheses that had previously relied solely on genetic comparisons.
Ancient Enzymes as Biotech Tools
The most immediate implications of the study are for biotechnology rather than evolutionary biology. When the researchers expressed ancient enzymes in microbial systems, they found that the reconstructed enzymes were often easier to use than those found in modern cannabis plants.
“What once seemed evolutionarily ‘unfinished’ turns out to be highly useful,” said Robin van Velzen, who led the study with colleague 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.”
Hellbound and Down 