Fungal secondary metabolism

Fungi are prolific producers of secondary metabolites, a diverse group of low-molecular-weight compounds that are not directly involved in growth, development, or reproduction but play critical roles when fungi interact with their environment. Secondary metabolites serve a wide array of ecological functions, including defense from abiotic stresses, inhibition of microbial competitors, or predator deterrence. When cultured with the necessary environmental cue(s), transcriptional and epigenetic regulatory networks lead to expression of the biosynthetic genes required for secondary metabolite production, which are often co-localized into biosynthetic gene clusters. Bioinformatic efforts have revealed that great biosynthetic potential exists across fungal genomes and is awaiting discovery. The challenge is that many biosynthetic gene clusters remain cryptic or silent under standard laboratory conditions. Fungal secondary metabolites have provided important chemistry for the medical, agricultural, and food sectors. Unlocking the hidden potential of silent biosynthetic gene clusters is the exciting future of research, which will lead to even more natural products to aid humanity. In this primer, we discuss biosynthesis, regulation, and ecology of fungal secondary metabolites, as well as future outlooks for secondary metabolite research (Figure 1).