| Streptomyces spp. are filamentous soil bacteria renowned for their morphological complexity and for their ability to produce a wide variety of secondary metabolites, of which antibiotics are most notable. A group of genes of Streptomyces coelicolor, the bld genes, are involved in the regulation of morphological differentiation, and many of these genes, including the bldG gene, are also required for antibiotic production. bldG and a downstream open reading frame (designated orf3) encode proteins showing similarity to anti-anti-sigma factors (e.g. SpoIIAA and RsbV) and anti-sigma factors (e.g. SpoIIAB and RsbW) of Bacillus subtilis, respectively. These proteins in Bacillus regulate the activity of sporulation- and stress-response-specific sigma factors that are encoded along with the cognate regulatory proteins. However, a sigma factor gene is not present in the vicinity of bldG and orf3 in S. coelicolor. An in-frame deletion mutant of bldG was constructed that showed the same phenotype as bldG point mutants, whereas deletion of the orf3 gene resulted in a variety of phenotypes with regards to morphological differentiation and antibiotic production, possibly due to the accumulation of secondary site mutations in the target sigma factor gene. In vitro phosphorylation assays demonstrated that, as with other anti-anti-sigma factors, BldG is likely regulated by phosphorylation, and a bldG mutant strain expressing the non-phosphorylatable BldG protein was unable to differentiate or produce antibiotics, suggesting that phosphorylation of BldG is necessary for proper development in S. coelicolor. DNA microarray experiments revealed a number of genes that may be transcribed by a BldG/ORF3-regulated sigma factor, including afsS, which encodes a global regulator of antibiotic production. Potential mechanisms for how BldG and ORF3 might function to regulate morphological and physiological differentiation in S. coelicolor are discussed. |
