Taxomyces andreanae, a fungal endophyte, was isolated from the phloem (inner bark) of the Pacific yew, Taxus brevifolia. The fungus is hyphomyceteous and, when grown in a semi-synthetic liquid medium, produced taxol and related compounds. Taxol was identified by mass spectrometry, chromatography, and reactivity with monoclonal antibodies specific for taxol. Both [1-14C]acetic acid and L-[U-14C]phenylalanine served as precursors of [14C]taxol in fungal cultures. No taxol was detected in zero-time cultures or in the small agar plugs used to inoculate the culture flasks.

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Berkeley Pit Lake is an abandoned open-pit copper mine filled with 30 billion gallons of acidic, metal-contaminated water. This harsh environment is proving to be a source of unusual microorganisms that produce novel bioactive metabolites. Bioassay-guided fractionation using signal transduction enzyme assays led to the isolation of the novel spiroketal, berkelic acid 1, and of the known gamma-pyrone, spiciferone A 4. Berkelic acid has shown selective, nanomolar activity against OVCAR-3, an ovarian cancer cell line in the National Cancer Institute cell line screen. The isolation and characterization of these compounds are reported here.

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-1-14C and phenylalanine UL-14C served as precursors of taxol-14C 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.

The antimicrobial metabolite of the marine sponge Smenospongia aurea was found to be 5-bromo-N,Ar-dimethyltryptamine (4). The same sponge also contained aureol ( 6), an unusual sesquiterpene-hydroquinone derivative. A second sample of S. aurea contained 8-epichromazonarol (20) and the indole 27. Two samples of Smenospongia echina were examined and were shown to contain the antimicrobial constituent 5,6-dibromo-M-N-dimethyltryptamine (3), with small amounts of the phenol 25 in one sample. The structure of aureol (6) was determined by X-ray analysis while those of the remaining compounds were determined from spectroscopic data, particularly 13C NMR spectra, and chemical interconversions.