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Lower-cost anti-tumor drug from yew needles

Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. : 12 December, 2004  (New Product)
Natural sources of the active principle used in the cancer drug Taxol are limited, and its chemical synthesis is complicated. A precursor can be produced simply and at low cost using an enzyme membrane reactor. The raw material is an extract derived from yew needles.
The bark of mature Pacific yew trees (Taxus brevifolia) conceals a valuable treasure: The potent anti-tumor drug paclitaxel, marketed under the name of Taxol. Oncologists use it to combat ovarian and breast cancer, and also to treat lung carcinomas. It gradually kills off cancerous cells by inhibiting cell division. Unfortunately, the yew is a slow-growing tree and only produces minute quantities of the drug. The complete chemical synthesis of paclitaxel is too complex to be cost-effective. Researchers have therefore long been searching for alternatives. The foliage of the cultivated European common yew (Taxus baccata), offers a viable starting point. It produces the compound 10-deacetylbaccatin III (DAB), from which Taxol can be synthesized in just a few steps. Researchers at the Institute for Bioprocessing and Analytical Measurement Techniques (iba) have developed a method for the biotechnological processing of DAB as part of a project, working in partnership with the Berlin University of Technology and the Institut fr Bioanalytik, Umwelttoxikologie und Biotechnologie Halle. The Fraunhofer Patent Center for German Research PST is overseeing the marketing of the project, along with the relevant patents.

'We use an enzyme isolated from the yew-needle extract to process the DAB,' explains Professor Gerald Lauckner of the iba. 'This produces baccatin III, a precursor to paclitaxel, which pharmaceutical companies can then employ to synthesize the final product.' The team has devised a low-cost process to produce the enzyme using a genetically modified strain of the bacterium E. coli. The bacteria are immobilized in the microscopic pores of a membrane. When a solution of DAB flows over the membrane in the reactor, it is converted to baccatin III. The product is separated using a halogen-free solvent, and any unconverted DAB is allowed to flow back into the reactor. An online analysis system continuously monitors and controls the inflow of DAB. The concentration is held at a constant level, thus raising the efficiency of the enzymatic reaction.

'The production cost is five times lower than for processes that extract the product from natural sources,' Lauckner insists. And there is still plenty of scope for further optimization. The researchers are now looking for industrial partners for this part of the project. 'When we find a suitable partner, we will be able to scale up the process,' states Lauckner. The present output of the iba laboratory prototype is about four grams per liter of reagent solution.
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