www.checkbiotech.org ; www.raupp.info ; www.czu.cz

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, March 2006.

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 be
used to produce second-generation versions of the drug. Walker said the
added advantage is that water-based chemicals rather than chlorinated
solvents can be used with his methods.

For reasons ranging from competitive advantage to corporate culture, or to a
desire to be a good corporate citizen, pharmaceutical companies are drawn to
finding ways to minimize their environmental footprint as they make
life-saving drugs.

"In fighting one pathological system, it makes sense to not create another
problem that can have a global effect," Walker said.

Plus, Walker said assessing the Taxol pathway enzymes opens doors to new,
more natural ways to make Taxol. He said that learning to genetically modify
the qualities of the Pacific yew organism to make tomorrow's versions of
Taxol could mean transferring all the genes - the entire pathway - into a
bacterium for large-scale production of the new and improved Taxol, without
further depleting the yew plant.

"Eventually, it will be cool when we're able potentially to have bacteria
make all of the necessary plant enzymes, and we can sit back and watch E.
coli make first- and second-generation Taxol molecules," Walker said.

[www.news-medical.net]

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