The orphan histidine kinase PdtaS-p regulates both morphological differentiation and antibiotic biosynthesis together with the orphan response regulator PdtaR-p in Streptomyces

In Streptomyces pristinaespiralis, the orphan histidine kinase (HK) PdtaS-p (encoded by SSDG_02492), which belongs to proteins of two-component systems (TCSs), plays an important role in both morphological differentiation and antibiotic biosynthesis. Owing to the isolated genetic organization of pdtaS-p, it is a challenge to identify its cognate response regulator (RR) and hampers the efforts to elucidate the regulation mechanism of PdtaS-p. In this study, based on bioinformatics analysis, we identify the cognate RR PdtaR-p (encoded by SSDG_04087) of PdtaS-p by phenotype similarity of gene deletion mutants as well as in vitro phosphor-transfer assay. We show that the mutants (.pdtaR-p and.pdtaS-p) exhibit almost the same phenotypical changes, showing a bald phenotype on MS agar and reduced pristinamycin biosynthesis. Further phosphor-transfer assay indicates that the phosphoryl group of HK PdtaS-p can be specifically transferred to RR PdtaR-p. Compared with the majority of RRs that harbor DNA-binding domains, PdtaR-p contains a putative ANTAR RNA-binding domain involved in controlling gene expression at the post-transcription level. Finally, we demonstrate that their ortholog from the model strain Streptomyces coelicolor, PdtaS-c/PdtaR-c, also regulates both morphological differentiation and antibiotics biosynthesis, suggesting that PdtaS-p/PdtaR-p-mediated molecular regulation may be conserved in the genus Streptomyces. To our knowledge, this is the first report describing the functional identification of ANTAR RNA-binding regulators in Streptomyces.