Finding genes to build a better cancer treatment

Scientists are one step closer to understanding how trees make the cancer drug Taxol.

In a recent article published in the Biological Chemistry Magazine, a group of researchers led by Mark Lange of Washington State University, have found candidate genes that could eventually be used to make Taxol more quickly and efficiently.

“Our goal is to find enzymes that activate precursors that contribute to the complex structure of Taxol,” said Lange, a professor at the WSU Institute of Biological Chemistry. “That will allow engineers to know which genes to include in the mix to develop organisms that can produce the drug.”

Also known as paclitaxel, Taxol is a natural compound discovered in the bark of Pacific yews.

It is used to treat a variety of cancers, from breast to ovarian, bladder, prostate, and more.

It used to be harvested directly from trees stripping their bark, but the harvests were not made sustainably and many of the trees died. Currently, most of the drug sold in the United States is produced by extracting the substance from laboratory-grown yew tree cell cultures.

This process is time consuming and expensive.

“We have been working on this for many years because Taxol’s structure is very complex,” said Lange. “There are more than 500 known natural taxane products, of which Taxol is just one. We are trying to find enzymes that activate precursors to produce Taxol, but not other taxanes.”

Enzymes are substances in living organisms that act as catalysts to initiate a chemical reaction.

“Ideally, you want an enzyme that triggers one specific reaction, rather than multiple reactions,” said Lange.

Other scientists will use these results to add genes to yeast or other microbes, allowing them to produce the drug in large quantities.

“It is very challenging,” Lange said. “It could involve 30 to 50 genes. But the genes we characterize here may be part of that.”

Lange and his team are part of a much larger group working on the project, including an engineer and biologists from Stanford University’s University of California system and the John Innes Center in the UK.

They received a $ 4 million grant from the National Center for Complementary and Integrative Health, part of the National Institutes of Health, last fall in support of the project.