Scientists produce cancer drug from common lab plant

Stanford scientists have used a common laboratory plant to produce a widely used cancer fighting drug - previously only available from an endangered Himalayan plant.

Scientists produce cancer drug from common lab plant
WASHINGTON: Stanford scientists have used a common laboratory plant to produce a widely used cancer fighting drug - previously only available from an endangered Himalayan plant.

The advance could lead to a more stable supply of the drug and allow scientists to manipulate that drug to make it even safer and more effective.

Elizabeth Sattely, an assistant professor of chemical engineering at Stanford, and her graduate student Warren Lau isolated the machinery for making the drug from an endangered plant.

They then put that machinery into a common, easily grown laboratory plant, which was able to produce the chemical.

In the study, published in the journal Science, Sattely and her team used a novel technique to identify proteins that work together in a molecular assembly line to produce the cancer drug.

Her group then showed that the proteins could produce the compound outside the plant - in this case, they had put the machinery in a different plant, but they hope to eventually produce the drug in yeast.
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Either the plant or yeast would provide a controlled laboratory environment for producing the drug.

This work could lead to new ways of modifying the natural pathways to produce derivative drugs that are safer or more effective than the natural source.

The drug Sattely chose to focus on is produced by a leafy Himalayan plant called the mayapple. Within the plant, a series of proteins work in a step-by-step fashion to churn out a chemical defense against predators.

That chemical defense, after a few modifications in the lab, becomes a widely used cancer drug called etoposide.
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The starting material for this chemical defense is a harmless molecule commonly present in the leaf. When the plant senses an attack, it begins producing proteins that make up the assembly line.

One by one, those proteins add a little chemical something here, subtract something there, and after a final molecular nip and tuck, the harmless starting material is transformed into a chemical defense.
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The challenge was figuring out which of the many proteins found in the mayapple leaf were the ones involved in this pathway.

Sattely started with the realisation that the proteins she needed to find were not always present in the leaf. "It's only when the leaf is wounded that the molecule is made," she said.

It turns out that after damaging the plant leaf, 31 new proteins appeared. Sattely and her team put various combinations of those proteins together until they eventually found 10 that made up the full assembly line.

They put genes that make those 10 proteins into a common laboratory plant, and that plant began producing the chemical they were seeking.
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