A Class 1 Histone Deacetylase as Major Regulator of Secondary Metabolite Production in Aspergillus nidulans.

摘要: An outstanding feature of filamentous fungi is their ability to produce a wide variety small bioactive molecules that contribute survival, fitness, and pathogenicity. The vast collection these so-called secondary metabolites (SMs) includes play role in virulence, protect from environmental damage, act as toxins or antibiotics harm host tissues, hinder microbial competitors for food sources. Many compounds are used medical treatment; however, biosynthetic genes the production natural products arranged compact clusters commonly silent under growth conditions routinely laboratories. Consequently, arsenal yet unknown fungal waiting be discovered. Here, we describe effects deletion hosA, one four classical histone deacetylase (HDAC) Aspergillus nidulans; show HosA acts major regulator SMs with converse regulatory depending on metabolite gene cluster examined. Co-inhibition all enzymes by pan HDAC inhibitor trichostatin A analysis double mutants indicate able override known other HDACs such class 2 type enzyme HdaA. Chromatin immunoprecipitation revealed direct correlation between hosA deletion, acetylation status H4 regulation SM genes, whereas H3 hyper-acetylation could not detected upregulated Our data suggest has inductive addition its repressor via deacetylation histones. Moreover, genome transcriptome SMs, expression several important protein categories carbohydrate metabolism proteins involved disease, defense significantly affected HosA.