5-Methylmellein is a novel inhibitor of fungal sirtuin and modulates fungal secondary metabolite production
| Autor: | Ryosuke Shigemoto, Takara Matsumoto, Shunsuke Masuo, Naoki Takaya |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Metabolite 030106 microbiology Secondary Metabolism Secondary metabolite Applied Microbiology and Biotechnology Microbiology Aspergillus nidulans 03 medical and health sciences chemistry.chemical_compound Polyketide Inhibitory Concentration 50 medicine Sirtuins Secondary metabolism Ascomycota biology Molecular Structure Chemistry Fungi biology.organism_classification Culture Media High-Throughput Screening Assays Histone Deacetylase Inhibitors 030104 developmental biology Biochemistry Isocoumarins Sirtuin biology.protein Histone deacetylase activity medicine.drug |
| Zdroj: | The Journal of general and applied microbiology. 64(5) |
| ISSN: | 1349-8037 |
| Popis: | Sirtuin is an NAD+-dependent histone deacetylase that is highly conserved among prokaryotes and eukaryotes. Sirtuin deacetylates histones and non-histone proteins, and it is involved in fungal growth and secondary metabolite production. Here, we screened 579 fungal culture extracts that inhibited the histone deacetylase activity of Sirtuin A (SirA), produced by the fungus Aspergillus nidulans. Eight fungal strains containing three Ascomycota, two Basidiomycota and three Deuteromycetes produced SirA inhibitors. We purified the SirA inhibitor from the culture broth of Didymobotryum rigidum JCM 8837, and identified it as 5-methylmellein-a known polyketide. This polyketide and its structurally-related compound, mellein, inhibited SirA activity with IC50 of 120 and 160 μM, respectively. Adding 5-methylmellein to A. nidulans cultures increased secondary metabolite production in the medium. The metabolite profiles were different from those obtained by adding other sirtuin inhibitors nicotinamide and sirtinol to the culture. These results indicated that 5-methylmellein modulates fungal secondary metabolism, and is a potential tool for screening novel compounds derived from fungi. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|