Natural products have a long history of providing novel compounds either directly or as lead compounds for human therapeutics, nutrition and agricultural applications. Fungal diversity has evolved over 900 million years and concurrent with this evolution is diversification of the natural product chemistry resulting in an impressive array of compounds known as specialized metabolites. In the organisms, natural products have biological activity to enable adaptation of the organism to its' ecological niche, ranging from profound effects of hormones to sometimes only the subtle effects observed under specific environmental conditions mediated by more specialized metabolites. In agricultural systems fungal metabolites can cause detrimental effects and large losses to agricultural crop yields, at the same time because of their biological activity these specialized metabolites can be translated for use as human therapeutics1-3. A significant renewed interest in mining fungi (and plants) for specialized metabolites is the availability of massive sequencing data and their potential for widespread use in agriculture, industry and as pharmaceutical agents.
The fungus Sclerotinia homoeocarpa is a widespread fungal pathogen, notable as the causal agent of dollar spot in turf grass 4- 6. It also produces novel nortetralabdane diterpenoids with potent antibacterial and insecticidal properties 7. Related fungi such as Sclerotinia sclerotiorum are persistent pathogens of agronomically relevant crops8. In general, the biological functions of the
majority of the fungal metabolites are unknown but are assumed to be an adaptation of the fungus to its biological niche. Regardless of the role, they have a diverse and useful chemistry 1. Our long-term goal is to understand the enzymatic diversity of natural product chemistry for the production of molecules with benefit to agriculture and human health. In this proposal our objective is to evaluate the terpene based natural products of S. homoeocarpa with an emphasis on deciphering the biosynthetic pathway nortetralabdane diterpenoids. This will be carried out through a combination of gene discovery and biochemical characterization of terpene related biosynthetic genes in the ascomycete fungus S. homoeocarpa, combined with metabolic studies in the wild -type and mutant variants. Phylogenetic analysis amongst related species will allow us to see the spread and distribution of metabolites and give us the arsenal to begin dissecting the roles of these in Sclerotinia and phylogenetically related fungi.
To help us achieve these aims we will employ a combination of a diverse set of tools including bioinformatics, comparative metabolomics, biochemical characterization of genes towards de novo pathway elucidation and structural determination by NMR of intermediary compounds.