The present proposition aims to :
- Collect and select species, varieties and cultivars of yew whose leaves contain as large amounts as possible of taxol, known or potential precursors. Specimens will be collected essentially in Ireland and France and their constituents will be analyzed by chemical and biological tests.
- Cultivate the species, varieties and cultivars thus selected under conditions allowing the mechanization of harvesting providing an alternate high value-added crop.
- Develop tissue and cell cultures of the selected specimens. Design an immunoassay technique for rapid detection of metabolites. The biotechnological production of taxol and/or biologically active analogs and precursors would provide valuable alternative route.
- Conceive new semisynthetic pathways towards taxol and analogs from newly identified precursor(s) extracted from leaves and/or tissue and cell cultures.
Taxol and its analogs are extremely complex molecules and in spite of recent sophisticated, chemically beautiful (but not economically) total syntheses, extraction from selected plants and semisynthesis will remain the method of choice for several decades. Thus the selection followed by the cultivation of yew in combination with progress in biotechnology and semisynthesis should provide Europe with a sufficient supply of this new type of anticancer drugs.
The toxicity of yew has been known since antiquity, but its cytotoxicity was discovered only in 1964 within the framework of a screening program for anticancerous natural products funded by the NIH (USA). The structure of the active compound - taxol - which is present in very small quantities, was determined in 1971. In 1979, the discovery that its biological activity was due to a novel mode of action led to intensive investigations; taxol is soon to be marketed as a drug under the brandname TAXOL by Bristol-Meyers Squibb.
Taxol is extracted from the bark of the American yew. Removing the bark kills the tree and it soon became evident that other sources had to be found. The discovery of an abundant precursor of taxol in yew leaves allowed the design of a semisynthesis of a new drug which should allow its production without ecological damage.
Funding SchemeCSC - Cost-sharing contracts