The researchers tested whether their new enzyme could modify a wide range of small aromatic molecules, ranging from plant flavonoids ?for instance, compounds found in hops that give beer its bitter taste or in other plants act as sunscreens, pigments, or antibiotics ?to olivetol, a component in the production of THC, the active ingredient of marijuana. Unlike other previously known prenylation enzymes that only act on a small number of molecules, this new enzyme was able to attach prenyl groups to most of the different aromatic compounds tested. Some of the newly-formed hybrid molecules had previously been found in natural sources, but the enzyme also built some new compounds that had never been seen before.
The key to Orf2’s flexibility seems to reside in the active site, the region of the enzyme where the small aromatic molecules bind. In many enzymes, the structure of the active site only allows one specific molecule to interact with it, like a key fitting into a lock. But the scientists found that Orf2’s active site is a surprisingly spacious barrel-like structure, unlike any protein fold ever seen before. Not only does this wide barrel allow Orf2 to act on such a wide range of aromatic molecules, its discovery could also shed new light on the relationship between an enzyme’s structure, the way it has evolved, and the chemical reactions it is able to carry out.
Although the researchers have not yet had a chance to test the modified molecules to see if their function has changed, they believe that Orf2 could be a powerful tool for creating biologically active compounds that could be used as drugs or as new methods of enhancing the disease-preventative properties of plants. Because the enzyme is able to modify such a wide range of compounds, scientists seeking to develop new drugs could use it in several different ways. If they had no particular end pr