Approaches and progress toward bioactive leads from fungi

Of the over 250,000 compounds that have been described from Nature, only about 15,000 of these have been from fungi. This is somewhat surprising, since fungi are ubiquitous and found throughout the world, able to thrive in almost any environment. Estimates predict between 1.5 and 5 million species of fungi, and there are likely even more. Yet, barely 100,000 have been studied in any detail. Fungi are prodigious chemists, and research suggests that each fungus can produce unique metabolites. Thus, the question is not “can fungi produce unique metabolites”; rather it is, “how does one sort the most promising fungi from those that produce known chemistries”. We probe this question daily, and my research team focuses on examining unique niches for under explored fungi, with the thought that unique biodiversity may reveal unique chemistry. Moreover, we prioritize samples by dereplicating them in situ, using techniques to analyze the chemistry of fungal cultures directly from Petri dishes. The process for sampling the surface of culture is based on an amalgamation of instrumentation, including a droplet-liquid-microjunction-probe coupled with UPLC-HRMS. For recent leads, the dereplication and scale up experiments have afforded some of the more pragmatic results, as they have provided materials for further pharmacological evaluation and medicinal chemistry development, even for bioactive fungal metabolites that were considered scarce.