Bacteria-induced activation of a fungal silent gene cluster is controlled by histone deacetylase Sirtuin E

Abstract

AbstractFilamentous fungi encode an untapped reservoir of natural products whose biosynthesis enzymes are often encoded by gene clusters. The majority of these gene clusters are only activated under distinct environmental conditions such as the presence of distinct neighbouring microorganisms but not under standard laboratory conditions. Previously, we provided evidence for such a scenario with the specific activation of the silentorsgene cluster in the filamentous fungusAspergillus nidulansby the bacteriumStreptomyces rapamycinicus. The bacterium triggered the activation of the GcnE histone acetyltransferase that acetylated histone 3 in nucleosomes of theorsgene cluster and thebasRtranscription factor, and thereby the gene cluster. The inducing compound was shown to be the bacterial arginoketide azalomycin F. Here, by inhibitor studies with the pan-sirtuin inhibitor nicotinamide (NAM) the involvement of a sirtuin HDAC was implied. Accordingly, deletion of all six putative sirtuin-encoding genes (sirA-EandhstA) revealed that only deletion ofsirEled to production of orsellinic acid byA. nidulanswithout the need of the bacterium. Also other effects on growth and colony morphology due to NAM were phenocopied by thesirEdeletion mutant. Addition of NAM did not compensate for the loss of the BasR transcription factor required for activation of theorsgene cluster. Collectively, SirE is the negative regulator of the bacteria-induced activation of theorsBGC. In line, addition of NAM to monocultures ofAspergillus mulundensisencoding a sirtuin E with highest similarity to theA. nidulansprotein also activated theorsBGC in this fungus.