Scientists Find New Way To Produce Common Cancer Drug Etoposide, Which Originally Came From Endangered Plants
For ages, we have been using plants as remedies for countless illnesses and ailments. To this day, even some of our more advanced medicines used to treat pain, cancer, and prevent diseases find their basis in plants, some of which are endangered. And even if these plants are rare, some drugs still rely on them as their primary ingredient, posing an issue researchers are intent on solving.
Dr. Elizabeth Sattely of Stanford University along with her graduate student, Warren Lau, have found one promising solution for recreating cancer-fighting ingredients in rare plants. By isolating the proteins and mechanisms used to create the chemicals essential to a distinct cancer drug, Sattely has been able to transfer these mechanisms into a common laboratory plant and have that plant produce the chemical. Sattely believes that by using this technique, the threat of the chemical becoming unavailable diminishes, while also allowing for a less expensive and more easily controlled source.
"People have been grinding up plants to find new chemicals and testing their activity for a really long time," Sattely said in a press release. "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."
For the study, published in the journal Science, Sattely and her team specifically looked at mayapple, a leafy Himalayan plant used to create the popular cancer drug etoposide. The desired chemical the team sought to study is produced when the plant is threatened, triggering a series of proteins to form an assembly line-like structure that produces the chemical for defense against predators.
The researchers already knew the molecule within the plant that starts the reaction; relatively harmless, the molecule springs into action when the plant is attacked, producing the proteins necessary to form the assembly line. Each individual protein will then work to add and subtract the necessary compounds to produce this chemical defense mechanism.
What Sattely and her team were tasked with doing first was finding which proteins were the ones responsible for the chemical. To figure this out, Sattely first needed to wound the leaf in order to trigger the reaction. Once the leaf was in defense mode, the team observed that 31 new proteins appeared at the injury site. The next step then involved putting different combinations of these proteins together until they found the 10 that made up the full assembly line. After the proteins were discovered, the team put the genes necessary to make these proteins into a common laboratory plant, and that plant started producing the chemical.
"A big promise of synthetic biology is to be able to engineer pathways that occur in nature, but if we don't know what the proteins are, then we can't even start on that endeavor," Sattely said.
Finding success in their first endeavor, Sattely says the next step is to try and synthesize this chemical in yeast. Sattely says that by putting the proteins in yeast, they will be able to grow the yeast in large vats within the lab, creating a bigger and more stable source of the chemical. Yeast will also allow the researchers to better modify different components of the process to possibly alter the drug, if necessary.
Sattely and Lau hope that their technique could be applied to other plants that are relied on to make other vital drugs.
“My interests are really identifying new molecules and pathways from plants that are important for human health,” she said.
Source: Sattely E, Lau W. Six enzymes from Mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science. 2015.