ABSTRACT: Extracytoplasmic function (ECF) sigma factors are a major type of bacterial signal transducer whose biological functions remain poorly characterised in streptomycetes. In this work, we studied SCO4117, a conserved ECF sigma factor from the ECF52 family, a class of ECF sigma factors exclusive to Actinobacteria. We demonstrate that SCO4117 is a pleiotropic activator of secondary metabolism, germination, aerial mycelium differentiation and sporulation. The expression of genes encoding secondary metabolism pathways (deoxysugar synthases, actinorhodin biosynthetic genes), and genes involved in differentiation (bld, whi, rdl, chp, nepA, ssgB, scbR), was dramatically reduced (up to 300-fold) in a SCO4117 knockout strain. SCO4117 expression depends on its position in the chromosome, as the knockout mutant phenotype can only be fully complemented when the SCO4117 ORF is restored in the chromosome. A strain expressing a truncated version of SCO4117 harbouring only the ECF sigma factor domain, has an opposite phenotype to that observed in the knockout strain, consisting of overproduction of antibiotics (actinorhodin, CDA, cryptic antibiotics) and acceleration of differentiation (aerial mycelium differentiation and sporulation), suggesting a complex interaction between the SCO4117 domains that affects protein activity. Some genes from predicted secondary metabolite clusters (cryptic pathways) were up-regulated compared to the wild strain, indicating that this truncated version of the SCO4117 protein might be useful to activate cryptic pathways. Overall, in this work we demonstrate the pleiotropic effects on the regulation of secondary metabolism and differentiation of SCO4117, the first member of the ECF52 family to be characterised. SCO4117 is a conserved gene overexpressed during the substrate and aerial mycelium stages, showing complex regulation at the transcriptional and post-translational levels.
