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Researchers advance biosynthesis of potent anti-cancer drug Taxol
Date:9/30/2010

MEDFORD/SOMERVILLE, Mass.--Researchers from Tufts University School of Engineering and MIT have reported a new way to biosynthesize important precursors to the potent anti-cancer compound Taxol in an engineered strain of E. coli bacteria.

The findings are significant steps on the way to achieving cost-effective, large-scale production of Taxol and the effort to design new Taxol-like pharmaceuticals.

The work is reported in the October 1, 2010, issue of the journal Science.

Taxol (paclitaxel) and its structural analogs are among the most powerful and commercially successful anticancer drugs, used to treat Kaposi's sarcoma and breast, lung and ovarian tumors.

Taxol was originally derived from the bark of the Pacific yew tree. Its anti-cancer properties were discovered more than 40 years ago.

But Taxol's power comes with an environmental price: Early stage production methods required sacrificing two to four fully grown trees for each patient. Alternative means of production such as using needles rather than bark still rely on slow, laborious plant-based processes. This limits production of Taxol itself and development of new derivatives that might be even more effective.

"This was the basis for our efforts to redirect biosynthesis through a simple, process-friendly bacterium like E. coli," explains Tufts' Blaine Pfeifer, Ph.D., assistant professor of chemical and biological engineering and co-corresponding author on the paper. "We faced a tremendous challenge because of the engineering needed first to 'equip' the E. coli cell to support Taxol biosynthesis and the subsequent protein engineering required to allow the first two steps in the Taxol biosynthesis scheme to be active within this new host."

The complex metabolic sequence that produces Taxol involves at least 17 intermediate steps and is not fully understood. The team's goal was to optimize production of the first two Taxol int
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Contact: Kim Thurler
kim.thurler@tufts.edu
617-627-3175
Tufts University
Source:Eurekalert

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