The Himalayan mayapple is an endangered plant species but humans need it because it naturally produces podophyllotoxin, a compound in etoposide used as chemotherapy drug for treating cancer in the ovaries, testes and lungs.
Obtaining the plant, which grows slowly and can be found as high as 4,000 meters above sea level, can be expensive and difficult but researchers appeared to have come up with a technique that would make it easier to get hold of the crucial chemical that the plant produces.
Warren Lau and Elizabeth Sattely, from the Stanford University, have isolated the machinery for producing podophyllotoxin from the poisonous plant and put that machinery into a common laboratory plant that can produce the chemical.
The technique has potentials for use in other plants and drugs and could also pave way for producing more stable and less expensive sources of drugs.
"What was striking to us is that with a lot of the plant natural products currently used as drugs, we have to grow the plant, then isolate the compound, and that's what goes into humans," Sattely said.
The researchers mapped out the poisonous plant and identifed which of its proteins help produce podophyllotoxin. The researchers noticed that the leaf produces the chemical when it is damaged as a form of defense against an attack so they punctured the leaves and found 31 new proteins appear.
The researchers then used a combination of techniques to determine which enzymes produce these proteins when the leaf was wounded and eventually came up with the 10-protein combo responsible for producing podophyllotoxin.
The proteins were then transferred to Nicotiana benthamiana, a close relative of the tobacco plant, which is easy to engineer and is widely used by plant biologists.
The researchers were able to show that the proteins could produce the compound in another plant but they look forward to producing the drug in yeast as this could offer controlled lab environment for the production of the drugs.
The study could pave way for new means of modifying natural pathways of producing derivative drugs that are not just safer but are also more effective compared with the natural source.
"Our results enable production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin," the researchers reported in their study published in the journal Science on Sept. 11.
