Cannabis produces a complex suite of bioactive compounds, including tetrahydrocannabinol (THC) and cannabidiol (CBD), but how these molecules evolved has long been a mystery. Now, new research has shed light on their origin story – and opened the door to innovative ways of harnessing these compounds for human medicine.
In modern cannabis varieties, the proportions of these cannabinoids vary widely and are largely determined by the activity of corresponding synthase enzymes. The enzymes are also highly specialized products of a long evolutionary process and today’s types are far removed from those that existed millions of years ago.
Using ancestral sequence reconstruction, which reconstructs ancient proteins from modern genetic data, the team resurrected cannabinoid-producing enzymes from early cannabis ancestors. When expressed in the lab, the enzymes revealed which cannabinoids they could produce – and how their activity differed from modern versions.
What they found was that, unlike today’s highly specialized enzymes that produce specific cannabinoids, these ancient types were generalists, capable of creating multiple compounds – including THC, CBD and CBC – from a common precursor.
“What once seemed evolutionarily ‘unfinished’ turns out to be highly useful,” said WUR researcher Robin van Velzen, who led the study with his 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.”
Read the full article at New Atlas
