Bioactive Metabolites of the Endophytic Fungi of Pacific Yew, Taxus brevifolia

Abstract

The endophytic microbes associated with the Pacific yew tree, Taxus brevifolia, were examined as potential alternative sources of the anticancer drug taxol, a secondary metabolite of the host organism. A novel fungus, Taxomyces andreanae, isolated from the inner bark of a yew tree growing in northwestern Montana, appears to produce taxol and other taxanes, in de novo fashion when grown in semi-synthetic liquid media. The presence of taxol 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-1-14C and phenylalanine UL-14C served as precursors of taxol-14C in fungal culture labeling studies, confirming the de novo synthesis of taxol 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. Fungal endophytes used in this study are further screened for additional biological activity following taxol/taxane analysis.