The Journal of General and Applied Microbiology
Online ISSN : 1349-8037
Print ISSN : 0022-1260
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5-Methylmellein is a novel inhibitor of fungal sirtuin and modulates fungal secondary metabolite production
Ryosuke ShigemotoTakara MatsumotoShunsuke MasuoNaoki Takaya
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2018 Volume 64 Issue 5 Pages 240-247

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Abstract

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.

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© 2018, Applied Microbiology, Molecular and Cellular Biosciences Research Foundation
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