S71: Mapping unchartered territory – sesquiterpenoid discovery in mushrooms

Basidiomycetes are known to produce a large number of secondary metabolites, in particular sesquiterpenes, the largest and most diverse class of natural products.  Many sesquiterpenes display antimicrobial and cytotoxic properties, yet only a few fungal terpene synthases have been characterized for their ability to produce these natural products.  We have adopted a genomic approach to discover, clone and functionally characterize eleven novel terpene synthases, and their associated biosynthetic enzymes, from Omphalotus olearius.  Our analyses have shown that a number of these terpene synthases adopt hitherto unseen cyclization mechanisms, and produce a diverse range of sesquiterpenes.  We have also built a predictive framework that will facilitate genome mining and bioprospecting for biologically active sesquiterpenes in all Basidiomycota.  Our framework has not only shed light upon a previously undiscovered wealth of natural products, it also lays a path for the discovery and bioengineering of enzymes that produce pharmaceutically relevant compounds.