Leaf litter associated fungi from South Africa to control fungal plant pathogens

Fungal genomes encode a huge biosynthetic potential to produce a wide diversity of chemical structures with valuable biological activities remaining silent or under-expressed with standard laboratory conditions. Fungal natural products provide numerous environmentally friendly properties that make them an attractive alternative to the use of synthetic pesticides for the control management of fungal diseases in plants. The main goal of this study was to explore the potential application of a library of natural products extracts from 232 diverse leaf litter associated fungi from South Africa for the discovery of new bio-fungicides. Fungal strains obtained from the MEDINA Fungal Collection were taxonomically classified following molecular and phylogenetic analyses, revealing a high diversity of fungal strains associated with leaf litter from endemic plants of South Africa. A previously designed library prepared following a specific OSMAC approach was employed in this work to evaluate the antifungal activity on a panel of four relevant fungal phytopathogens, using a recently developed HTS platform. The presence of the epigenetic modifier suberoylanilide hydroxamic acid (SAHA) during fungal fermentations in specific formulation media determined considerable changes in the metabolomic profiles that clearly influenced the diversity and quantity of bioactive metabolites, which also affected the activity hit-rates. As a proof of concept, we describe herein the discovery of the novel molecule libertamide upon the addition of SAHA during the fermentation of the strain Libertasomyces aloeticus CF-168990. Libertamide showed antifungal potential to control Zymoseptoria tritici, the causal agent of septoria leave blotch. As result of the study, we show that leaf litter from South Africa is still an untapped source of new fungal species with large biosynthetic potential to produce promising candidates for the discovery of new natural fungicides.