Genetic engineering turns a plant into a Cancer Drug

Researchers report today that they’ve engineered a common laboratory plant to produce the starting material for a potent chemotherapy drug originally harvested from an endangered Himalayan plant. The new work could ensure an abundant supply of the anticancer drug and make it easier for chemists to tweak the compound to come up with safer and more effective versions. The Himalayan Mayapple (Podophyllum hexandrum). The short, leafy plant was the original source of podophyllotoxin, a cytotoxic compound that’s the starting point for an anticancer drug called Etoposide. The drug has been on the U.S. market since 1983 and is used to treat dozens of different cancers, from lymphoma to lung cancer. Today, podophyllotoxin is mainly harvested from the more common American Mayapple. Researchers did know was that podophyllotoxin isn’t always present in the plant. “It’s only when the leaf is wounded that the molecule is made,” says Elizabeth Sattely, a chemical engineer at Stanford University in Palo Alto, California, who led the current research effort.
The researchers then narrowed the likely candidates for enzymes in podophyllotoxin production by focusing on members of four classes known to carry out the right types of chemical reactions. They then spliced genes for each of these enzymes into bacteria known to infect Nicotiana benthamiana, a fast-growing relative of tobacco. Tthey eventually hit on a group of 10 enzymes that allowed the plant to make a molecule called desmethyl-epipodophyllotoxin, a direct precursor to Etoposide and a potent cancer drug.  Eventually, the new work will give drug companies a stable, abundant supply of their cancer-fighting drug, and it may give rise to similar compounds that could work even better.