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Tweaking Taxol points way to a greener, more productive future

As the effective cancer-treatment drug Taxol enters its next generation, Michigan State University announces discoveries which point to both environmentally friendly ways to produce more Taxol, and ultimately innovations to produce a more potent second-generation drug.

Kevin Walker, a chemistry and biochemistry and molecular biology assistant professor, in the March 24 issue of Chemistry & Biology, reports a step toward manufacturing more-potent Taxol molecules that could potentially reduce treatment dosages. The methods described minimize dangerous chemical usage, and put E.coli to work in the production process.

"We're trying to develop a biosynthetic process for the drugs that circumvents the use of organic solvent-based methods requiring costly waste management," Walker said. "This attempt is a green chemistry approach to produce more potent versions of Taxol."

Taxol generically known as paclitaxel is a top-selling cancer-fighting drug. It's most commonly used against ovarian and breast cancers, but currently is used in certain aspects of heart disease treatment, and is showing promise in Alzheimer's therapy.

Taxol is derived in small quantities from the Pacific yew tree. To fulfill large-scale production, pharmaceutical companies isolate, from the tree, an abundant natural product that is synthetically converted to Taxol in the laboratory.

Now, as abundant molecules from the yew are being synthetically modified for new, more potent versions of Taxol, Walker, along with Catherine Loncaric, a visiting research associate, and undergraduate Erin Merriweather, is looking for alternative, biological routes to introduce the modifications. Walker's laboratory makes use of recently identified genes of the yew that produce enzymes that craft the pathway to Taxol. The targets: five enzymes that biosynthetically decorate the core of the Taxol molecule.

The enzymes in natural and, potentially, genetically modified form can
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