AN INTERESTING DEVELOPMENT...

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Greetings --

It seems good things come in yucky packages; penicillin, and now epothilone.

Rosy

Scientists Squeeze Cancer Killer From Dirt

Updated 5:29 PM ET January 27, 2000

By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) - For years, doctors have known that a slimy bacterium

found in the dirt produces compounds that have strong effects against cancer.

But while the compounds, known as epothilones, are found literally underfoot,

they cannot be produced in the lab in any great amounts.

On Thursday, a small California biotechnology company said it had figured out

how to produce large amounts of the substance by genetically engineering

another bacterium.

Li Tang and colleagues at Kosan Biosciences in Hayward, California, said

their bacteria literally pump out epothilones.

" It should not take long now to develop our strain into one that produces the

amounts of epothilone needed for clinical trials, " Santi, one of the

founders and chairman of Kosan, said in a statement.

Epothilones have long been considered the natural successor to Taxol,

Bristol-Myers Squibb's powerhouse cancer drug. Based on compounds found in

yew trees, Taxol is especially efficacious against ovarian cancer.

" Although Taxol is the largest revenue anti-cancer agent in history, it has

two major shortcomings, " Kosan said in a statement. " First, many cancers are

resistant to the drug. "

Also, Taxol does not dissolve in water, so to infuse it into a patient, other

chemicals must be added. These can have side-effects. " For these reasons,

epothilone is widely perceived as a potential successor to Taxol, " the

statement read.

But it is hard to grow. The bacteria that naturally produce it live in slimy

colonies on the ground, and when grown in laboratory dishes cannot be coaxed

to produce more than a little bit of precious epothilone.

Writing in the journal Science, Tang and colleagues described how they found

the genes for epothilone A and B and spliced them into another bacterium,

Streptomyces coelicolor.

" S. coelicolor is more amenable to metabolic engineering and strain

improvement and grows about 10-fold as rapidly as the natural producer,

thereby offering the opportunity to develop a practical production system, "

Kosan said.

The company, which got a grant from the National Cancer Institute to do the

work, said it will now try to manipulate epothilones even more, to see if

they can find a way to make it even more effective against cancer.

Annual sales of Taxol, known generically as paclitaxel, and Taxotere, a

related drug made by Aventis, were $1.6 billion in 1998, with total sales

expected to grow to over $2 billion in 2000, Kosan said.

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