THE SEARCH FOR A TAXOL-PRODUCING MICROORGANISM AMONG THE ENDOPHYTIC FUNGI OF THE PACIFIC YEW, TAXUS-BREVIFOLIA

Endophytic microbes associated with the Pacific yew tree, Taxus brevifolia, were examined as potential sources of the anticancer drug taxol [1], a secondary metabolite of the host organism. The first promising organism found was the novel fungus, Taxomyces andreanae, which was isolated from the inner bark of a yew tree growing in northwestern Montana. It appears to produce taxol and other taxanes in de novo fashion when grown in semi-synthetic liquid media. The presence of 1 in the fungal extract was confirmed by mass spectrometry, comparative chromatographic behavior with ''yew'' taxol, reactivity with taxol-specific monoclonal antibodies, and 9KB cytotoxicity studies. Both acetate-1-C-14 and phenylalanine UL-C-14 served as precursors of taxol-C-14 in fungal culture labeling studies, confirming the de novo synthesis of 1 by the fungus. Immunoassay techniques are currently being used to screen extracts of Taxomyces andreanae for new taxanes, and to determine if other endophytic fungi are taxol producers.