Stanford researchers have engineered the easy-to-grow tobacco plant to produce small amounts of a starting chemical, or ‘precursor’ on which a particular cancer drug is based, one normally derived from an endangered plant. Their work, published on Sept 10th in Science Magazine suggests a potentially more efficient and sustainable way to obtain the drug, and their methodology, pinpointing the mechanism by which the endangered plant produces the precursor, may prove useful in the study of other plant-derived drugs.
Assistant professor of chemical engineering Elizabeth Sattely and her fifth-year graduate student Warren Lau began studying the widely used, plant-based cancer drug called etoposide two years ago. Etoposide is used in chemotherapy to target and kill suspiciously active cells and relies upon a chemical defence compound produced by a rare Himalayan plant, the mayapple. If Sattely and Lau could understand the mayapple’s defense mechanism, they reasoned, they might be able to replicate the same defense chemical in a more accessible organism.
Sattely and Lau first needed to determine which of the mayapple’s genes were responsible for producing the compound. However, the plant’s large number of genes made testing each individual gene inefficient. The researchers determined a more focused strategy: wounding the plant with a needle to activate its defences and then observing what new chemicals appeared. This narrowed the number of gene candidates to a manageable 31. After identifying the relevant genes, Sattely and Lau transferred them to a tobacco plant using a technique called transient expression system. According to Lau, tobacco was a ‘model organism’ for use in the study since it is simple to grow and has been widely studied.
They found tobacco successfully synthesized small amounts of the precursor, and the relevant proteins remained present in the plants for at least five days. Lau said that he and Sattely are still exploring ways to increase the amount of drug precursor produced, as well as ways to produce the precursor in different organisms. Currently, the most promising candidate is yeast. Not only are scientists familiar with cultivating it, yeast also allows researchers to modify drug precursors in ways that plants do not support. Read full article
H Knowles (28 September 2015) Stanford researchers engineer tobacco plant to produce cancer drug precursor [editorial]. Retrieved from http://ow.ly/SKWA7