The tobacco plant could be the source of new drugs to treat cancer.
Scientists have genetically engineered Nicotiana benthamiana (tobacco) to create an extract that outperforms the basis of the chemotherapy drug etoposide.
At the moment drugs manufacturers rely on the endangered Mayapple to get podophyllotoxin, which is key to the treatment, but it grows very slowly and only in the Himalayas.
So the researchers focused on four genes that are known in the production of podophyllotoxin, and then analyzed genetic data of the Mayapple to identify similar ones.
They then manipulated tobacco (Nicotiana benthamiana) to express multiple gene candidates at once and identified the resulting compounds in leaf tissue.
In total, the authors identified six new genes that, combined with the original four, produce the immediate etoposide precursor, desmethyl-epipodophyllotoxin, which outperforms podophyllotoxin as a chemotherapy ingredient.
Professor Elizabeth Sattely and her graduate student Warren Lau, of Stanford University, California, said podophyllotoxin, a chemical from Mayapple, is the natural precursor to etoposide, which is “used in dozens of chemotherapy regimens for a variety of malignancies.”
The work, published in the journal Science, may lead to a more stable supply of the drug and allow scientists to make it even safer and more effective.
Many of the drugs we take today to treat pain, fight cancer or thwart disease were originally identified in plants, some of which are endangered or hard to grow. In many cases, those plants are still the primary source of the drug.
The researchers have isolated the machinery for making the widely used cancer-fighting drug from an endangered plant and put that machinery into tobacco which was able to produce the chemical. The technique could potentially be applied to other plants and drugs
Prof Sattely said: “People have been grinding up plants to find new chemicals and testing their activity for a really long time. What was striking to us is with a lot of the plant natural products currently used as drugs, we have to grow the plant, then isolate the compound, and that is what goes into humans.”
They hope to eventually produce the drug in yeast. Either the plant or yeast would provide a controlled laboratory environment for producing the drug.
Prof Sattely said: “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 endeavour.”
Source: Mirror
Source: Mirror
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