Accessing the unuque terpenoid natural products portfolios of Basidiomycota

Basidiomycota and Ascomycota represent the major phyla of the fungal kingdom which is estimated to be comprised of more than 1.5 mio species. Only a fraction of this diversity has been described. Ascomycota have so far received the greatest attention by scientists and for applications in biotechnology while Basidiomycota remain greatly understudied despite their importance for e.g. carbon recycling and their medicinal properties. Homology-based analysis of fungal genomes for known natural products biosynthetic genes together with information on isolated natural products suggests that the secondary metabolome of Basidiomycota differs from those of other prolific microbial natural products producers. Sesquiterpene synthases appear to be the most abundant class of natural products scaffold generating enzymes in these fungi. Leveraging genomic information, we have identified and characterized more than 20 different sesquiterpene synthases from Basidiomycota. Many of the sesquiterpene synthases are located in associated biosynthetic gene clusters which we have begun to characterize. More recently, we have sequenced additional Basidiomycota genomes that give us access to new types of sesquiterpene scaffolds and clustered biosynthetic genes. As part of our efforts in mapping the sesquiterpene synthase portfolios in fungi, we have also discovered a Basidiomycota-specific sesquiterpene synthase in an endophytic Ascomycete that may have been acquired by horizontal gene transfer. This presentation will provide an overview of our efforts in characterizing and accessing the sesquiterpenoid natural products portfolio Basidiomycete fungi using genomics driven approaches together with heterologous expression and biochemical characterization of enzymes and biosynthetic pathways.