The regulatory gene wblA is a target of the orphan response regulator OrrA in Streptomyces coelicolor

Our previous study using transposon mutagenesis indicated that disruption of the putative response regulator gene orrA impacted antibiotic production in Streptomyces coelicolor. In this study, the role of OrrA was further characterized by comparing the phenotypes and transcriptomic profiles of the wild-type S. coelicolor strain M145 and Delta orrA, a strain with an inactivated orrA gene. Chromatin immunoprecipitation using a strain expressing OrrA fused with FLAG showed that OrrA binds the promoter of wblA, whose expression was downregulated in Delta orrA. The interaction of OrrA with the wblA promoter was further validated by a pull-down assay. Similar to Delta orrA, the deletion mutant of wblA (Delta wblA) was defective in development, and developmental genes were expressed at similar levels in Delta orrA and Delta wblA. Although both OrrA and WblA downregulated actinorhodin and undecylprodigiosin, their roles in regulation of the calcium-dependent antibiotic and yellow-pigmented type I polyketide differed. sco1375, a gene of unknown function, was identified as another OrrA target, and overexpression of either sco1375 or wblA in Delta orrA partially restored the wild-type phenotype, indicating that these genes mediate some of the effects of OrrA. This study revealed targets of OrrA and provided more insights into the role of the orphan response regulator OrrA in Streptomyces.