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

Summary

Scientists have discovered about 30,000 fungal compounds with useful properties, from life-saving antibiotics like penicillin to cholesterol-lowering drugs. However, new research suggests that fungi actually produce somewhere between 1.4 million and 4.3 million different chemical compounds, meaning we’ve only discovered about 1-2% of what’s out there. By studying the genomes of fungi, researchers estimate that for every fungal medicine we know about, there could be 50-100 more waiting to be discovered, representing an enormous opportunity for developing new drugs and therapies.

Background

Approximately 30,000 fungal secondary metabolites (SMs) have been characterized and are vital to the bioeconomy, including pharmaceuticals, food colorants, and cosmetics. SMs are biosynthesized by biosynthetic gene clusters (BGCs) organized in close physical proximity in the genome. The bulk of these SMs are produced by filamentous fungi in the Pezizomycotina subphylum of Ascomycota.

Objective

To estimate the total number of fungal secondary metabolites produced by filamentous fungi in the Pezizomycotina subphylum using rarefaction analyses and data from the well-characterized genus Aspergillus. The study aimed to gauge the magnitude of chemodiversity and undiscovered fungal metabolites across this large fungal subphylum.

Results

Analysis of 135 Aspergillus genomes revealed 6,972 putative BGCs grouping into 4,463 GCFs, with an estimated ~11,500 GCFs across 450 known Aspergillus species. Using 1.57 SMs per BGC, Aspergillus likely contains ~18,055 SMs. Scaling to the ~85,000 known Pezizomycotina species, the subphylum is estimated to harbor 1.4-4.3 million SMs from 870,000 to 2.7 million GCFs.

Conclusion

The vast majority of fungal secondary metabolites remain undiscovered, with current estimates suggesting 50-100 additional unknown SMs for every one known SM. Considering that only 5% of fungal species have been described and true Pezizomycotina diversity may exceed one million species, the projected number of fungal SMs could reach 16-50 million. These findings highlight the immense untapped potential for discovery of novel bioactive compounds with applications in medicine, agriculture, and industry.
  • Published in:mBio,
  • Study Type:Computational analysis, Predictive modeling,
  • Source: PMID: 40956095, DOI: 10.1128/mbio.01381-25
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