Bioactive compounds from four endophytic Penicillium sp. of a northwest pacific yew tree

In 1993, we reported an interesting phenomenon: a novel endophytic fungus isolated from the inner bark of the Northwest Pacific yew tree was able to synthesize taxol in denovo fashion. Taxol is an important new chemotherapeutic agent with unusual efficacy against the deadly and refractory breast and ovarian cancers. Unfortunately, taxol was originally isolated from the bark of the yew tree, which was in short supply. If a fungal producer of taxol were found, it could theoretically generate an unlimited supply of this new drug without encroaching on the dwindling populations of the yew tree. Following the discovery of the first taxol-producing fungus, several other endophytes were also found that appeared to produce taxoids, based on monoclonal antibody immunoassay, chromatographic analysis and mass spectral analysis. One of these fungi, identified as Penicillium raistrickii H10BA2, appears to make taxol and other taxanes in de novo fashion. But this Penicillium, and three other unidentified endophytic Penicillium sp., produce other secondary metabolites with pharmaceutical potential, which could eventually rival taxol in importance. Media composition is a critical aspect of fungal metabolite production. Endophytic fungi may respond chemically to host plant metabolites. Microorganisms often produce secondary metabolites in response to specific nutrients or environmental stress. This stress can be chemically induced by media manipulation, resulting in the production of unique metabolites. Varying fermentation protocols in synthetic media can affect the production and diversity of secondary metabolites. With this in mind, the secondary metabolites of these endophytes were examined in both conventional and "extreme" fermentation media.