mGem: How many fungal secondary metabolites are produced by filamentous fungi? Conservatively, at least 1.4 million

The ~30,000 known fungal secondary metabolites (SMs) are a vital component of the bioeconomy. SMs are biosynthesized by biosynthetic gene clusters (BGCs), i.e., sets of genes in close physical proximity in the genome. The bulk of these SMs are produced by filamentous fungi in the Pezizomycotina subphylum (phylum Ascomycota). To gauge the magnitude of chemodiversity in this subphylum, we utilized data from the well-characterized genus <i>Aspergillus</i> and a previous Pezizomycotina genomic survey. With 30-50 BGCs per genome, our rarefaction analyses show that the ~85,000 known species in Pezizomycotina likely contain 1.4-4.3 million SMs from an estimated 870 thousand to 2.7 million gene cluster families. Considering that only 5% of fungal species have been described and that the actual number of Pezizomycotina species is likely closer to a million, the projected number of SMs is likely between ~16 and 50 million. These estimates suggest that most fungal SMs remain undiscovered.