Fungal secondary metabolism: regulation, function and drug discovery

One of the exciting movements in microbial sciences has been a refocusing and revitalization of efforts to mine the fungal secondary metabolome. The magnitude of biosynthetic gene clusters (BGCs) in a single filamentous fungal genome combined with the historic number of sequenced genomes suggests that the secondary metabolite wealth of filamentous fungi is largely untapped. Mining algorithms and scalable expression platforms have greatly expanded access to the chemical repertoire of fungal-derived secondary metabolites. In this Review, I discuss new insights into the transcriptional and epigenetic regulation of BGCs and the ecological roles of fungal secondary metabolites in warfare, defence and development. I also explore avenues for the identification of new fungal metabolites and the challenges in harvesting fungal-derived secondary metabolites. In this Review, Nancy P. Keller describes the classification and genetics of secondary metabolites and biosynthetic gene clusters, cluster regulation and the ecological roles of secondary metabolites, and she explores avenues for the discovery of new fungal metabolites and current challenges in their identification.