S157: Mushroom hunting using bioinformatics – Terpenoid pathway discovery in Basidiomycota

Basidiomycota (aka. mushrooms) represent a diverse, yet largely uncharacterized, source of natural products. Sesquiterpenoids are the largest and most diverse class of secondary metabolites produced by these fungi; many of these compounds exhibit potent antimicrobial and cytotoxic properties. Yet, despite this apparent wealth of diversity, only a small fraction of basidiomycota has been studied for their production of bioactive secondary metabolites. Studies aimed at identifying biosynthetic enzymes and pathways so far are limited to only a handful of examples. We have characterized a suite of sesquiterpene synthases with novel cyclization mechanisms from the anticancer illudin producer Omphalotus olearius. This genome based approach facilitated development of a predictive framework for genome mining and bioprospecting for novel biological active sesquiterpenes in all Basidiomycota. Our framework has enabled the selective identification of novel sesquiterpene synthases and associated biosynthetic enzymes for bioengineering of these pathways into heterologous expression hosts.