MYCOLab Ai Logo - gold and army green

Tracing the Origin and Evolution of the Fungal Mycophenolic Acid Biosynthesis Pathway

Summary

Mycophenolic acid is an important drug that helps transplant patients by preventing their immune systems from rejecting new organs. Scientists studied the genes that fungi use to make this drug and found it in several fungal species. They discovered that this ability to produce the drug evolved a long time ago in fungi but was lost in most species over time, remaining only in a few special fungi.

Background

Mycophenolic acid (MPA) is a powerful immunosuppressant drug administered to millions of transplant recipients worldwide. MPA production is restricted to a limited number of filamentous fungi, and little is known about its biosynthetic modalities and evolutionary origin.

Objective

This study aimed to decipher the origin and evolution of the fungal MPA biosynthetic pathway by performing large-scale genomic analysis of fungal resources and phylogenomic analysis to identify MPA producers and understand the distribution and evolution of MPA biosynthetic gene clusters.

Results

Complete and functional MPA biosynthetic gene clusters were identified in Penicillium, Aspergillus, and Paecilomyces species. Phylogenomic analysis suggests the MPA cluster originated early in Aspergillaceae ancestors but was repeatedly lost. All MPA fungal producers showed resistance to MPA through different molecular mechanisms involving IMPDH gene dosage and expression levels.

Conclusion

This study provides unprecedented insight into the origin, distribution, and evolution of MPA biosynthesis in fungi. While the origin of the MPA gene cluster remains enigmatic, the findings indicate MPA biosynthesis likely appeared early in fungal evolution and was retained in specific lineages, supporting the role of this compound in fungal ecology.
  • Published in:Genome Biology and Evolution,
  • Study Type:Genomic and Phylogenetic Analysis,
  • Source: 10.1093/gbe/evaf039; PMID: 40052422
Scroll to Top