Unearthing fungal chemodiversity and prospects for drug discovery

Natural products have drastically improved our lives by providing an excellent source of molecules to fight cancer, pathogens, and cardiovascular diseases that have revolutionized medicine. Fungi are prolific producers of diverse natural products and several recent advances in synthetic biology, genetics, bioinformatics, and natural product chemistry have greatly enhanced our ability to efficiently mine their genomes for the discovery of novel drugs. In this article, we provide an overview of improved heterologous expression platforms for targeted production of fungal secondary metabolites, of advances in chemical and bioinformatics dereplication, and of novel bioinformatic platforms to discover biosynthetic genes involved in the production of metabolites with specific bioactivities. These advances, coupled with the presence of vast numbers of biosynthetic gene clusters in fungal genomes whose natural products remain unknown, have revitalized efforts to mine the fungal treasure chest and renewed the promise of discovering new drugs.