Unlocking the natural products potential of Basidiomycota - commonly known as mushrooms

Current estimates of fungal diversity exceed that of land plants by a ratio of 10:1. Higher fungi (Basidiomycota and Ascomycota) are known to synthesize an array of bioactive compounds and mushroom-forming fungi have been used for millennia in traditional medicine. It is thought that mushrooms are among the greatest resources for the discovery of novel biologically active compounds. Yet, despite their extremely rich chemodiversity and the prospects for the discovery of new drugs, only a small fraction of the Basidiomycota has been studied for natural products (NPs) production, and only a handful of studies have characterized their biosynthetic enzymes and pathways. Comprehensive studies are challenging, owing to the fact that it can be difficult or even impossible to cultivate many mushrooms under laboratory conditions. Recently, a large number of fungal genomes have been sequenced, due in part to an interest in fungi as sources of lignocellulose-degrading enzymes. The rapidly increasing availability of fungal genome data offers a tremendous opportunity for bioinformatics-guided approaches to uncover a largely untapped NP source.

Analysis of genomic information and a survey in SciFinder indicate that while polyketides and non-ribosomal peptides are clearly the major classes of NPs made by filamentous fungi, Basidiomycota seem to have evolved terpenoids as their major NPs group. Sesquiterpenoids are the largest class of secondary metabolites produced by these fungi; many of these compounds exhibit potent antimicrobial and cytotoxic properties. We have begun to investigate the terpenoid NPs diversity of these higher fungi, which will be discussed in this lecture.