Polyamine Induction of Secondary Metabolite Biosynthetic Genes in Fungi Is Mediated by Global Regulator LaeA and α-NAC Transcriptional Coactivator: Connection to Epigenetic Modification of Histones

Summary

Polyamines are natural compounds that act like chemical switches controlling how fungi produce useful medicines like antibiotics and statins. These molecules work by attaching to DNA and modifying histone proteins, which turns on or off the genes responsible for making pharmaceutical compounds. This research reveals that understanding polyamine control could help scientists increase antibiotic production and make plants more resistant to fungal diseases.

Background

Polyamines are polycationic compounds present in all living cells that regulate DNA replication and gene expression through nucleosome condensation and histone modifications. Filamentous fungi produce diverse secondary metabolites with pharmaceutical applications, but most biosynthetic gene clusters are silent or poorly expressed. Recent evidence indicates polyamines control secondary metabolite biosynthesis through epigenetic mechanisms.

Objective

This review examines the molecular mechanisms by which polyamines, particularly spermidine and 1,3-diaminopropane (DAP), regulate secondary metabolite biosynthesis in fungi through the global regulator LaeA and the α-NAC transcriptional coactivator. The article synthesizes advances in understanding plant-fungi interactions and epigenetic modifications of histones.

Results

Polyamines induce expression of the global regulator LaeA and increase formation of α-NAC transcriptional coactivator, controlling the switch from primary growth to secondary metabolite production. DAP and spermidine regulate biosynthesis of penicillin, cephalosporin, lovastatin, aflatoxins, and trichothecenes. Spermidine extends yeast lifespan and prolongs penicillin gene transcript half-life, effects correlated with vesicle formation and histone acetylation patterns.

Conclusion

Polyamines regulate fungal secondary metabolite biosynthesis through coordinated action on histone modifications, LaeA expression, and α-NAC coactivator formation. The α-NAC protein also induces plant resistance to fungal infections and systemic acquired resistance. Understanding these mechanisms has implications for improving secondary metabolite production and plant-fungi interaction management.
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