Exploiting the inconspicuous xylariaceous fungi as prolific sources for the discovery of new natural products

Since the late 19^th century, the fungi have earned a privileged pedigree among natural products producing organisms and have contributed some of the most important chemicals employed as human medicines and agrochemicals. Yet, a continuing need exists for innovative chemistry that blocks the development and progression of human diseases by targeting emerging targets in core pathways in cancer, emerging opportunistic pathogens, and multi-resistant pathogens. During the mid 20^th century, fast-growing fungi from soils were screened intensely for biologically active compounds. However, as this source became heavily exploited, the chances to find new natural products became increasingly difficult. Subsequently, ecology- and systematics-directed screening approaches have been applied as alternative strategies. As a result, new “hotspots” of natural product producers have been revealed, including a family of wood-inhabiting fungi called the Xylariaceae. So far, more than 500 compounds, often with striking biological activity, have been isolated from cultures and fruiting bodies of the estimated 10000 species in this family. The majority of these have been obtained from temperate taxa. In our ongoing work, we have focused on tropical and subtropical species. Spore-derived cultures and stromata were extracted and analyzed by HPLC for the occurrence of new natural products. Subsequently, more than 40 new chemical entities of various biosynthetic pathways have been isolated and biologically characterized. This presentation will illustrate the under-exploited potential for finding new secondary metabolites within the Xylariaceae.