A Possible Extended Family of Regulators of Sigma Factor Activity inStreptomyces coelicolor

Abstract

SCO4677 is one of a large number of similar genes in Streptomyces coelicolor that encode proteins with an HATPase_c domain resembling that of anti-sigma factors such as SpoIIAB of Bacillus subtilis. However, SCO4677 is not located close to genes likely to encode a cognate sigma or anti-anti-sigma factor. SCO4677 was found to regulate antibiotic production and morphological differentiation, both of which were significantly enhanced by the deletion of SCO4677. Through protein-protein interaction screening of candidate sigma factor partners using the yeast two-hybrid system, SCO4677 protein was found to interact with the developmentally specific Bacteria of the genus Streptomyces are highly adapted to living in soil environments and produce various valuable secondary metabolites. Their complex life cycle of morphological and physiological differentiation requires elaborate regulatory systems (6). The genome of the model species Streptomyces coelicolor A3(2) encodes 7,825 theoretical proteins, with more than 12% (Ն900 gene products) encoding transcriptional regulators. The 65 sigma factors of S. coelicolor strikingly point to the complexity of its gene regulation (ScoDB at http: //strepdb.streptomyces.org.uk) (2).Sigma factors have been found to be important for differentiation. BldN and N are required for formation of aerial hyphae (3,8), while WhiG initiates the formation of spores from aerial hyphae (5): bldN, sigN, and whiG appear to be transcribed throughout aerial mycelium formation and development. On the other hand, F is involved in the later stages of spore formation, and sigF transcription was detected only when sporulation started, and depended upon whiG and other early sporulation genes (whiA, whiB, whiH, whiI, and whiJ) (28). A sigF-null mutant formed smaller spores compared to the wild-type strain, with the spore wall being much thinner, and the chromosomal DNA of the sigF mutant was much less condensed (43). Among the seven other

BldG and SCO3548 Interact Antagonistically To Control Key Developmental Processes inStreptomyces coelicolor

“…The possibility that the BldG system involves additional anti-sigma factors therefore must be examined further. As previously discussed (32), analysis of these interactions may prove to be difficult due to the apparent promiscuity of the interactions between the many anti-antisigma factors and anti-sigma factors in S. coelicolor.…”

“…In M. tuberculosis, F activity is regulated by a single coexpressed anti-sigma factor, which is in turn antagonized by two distantly encoded anti-anti-sigma factors (4). As well, the F sporulation factor of S. coelicolor is regulated by an anti-sigma factor (RsfA) and at least two anti-anti-sigma factors, all encoded at separate loci (32). The presence of 45 additional RsbW orthologues in the S. coelicolor genome (45) provides a plethora of possible alternative binding partners for BldG.…”

The RNA Polymerase Omega Factor RpoZ Is Regulated by PhoP and Has an Important Role in Antibiotic Biosynthesis and Morphological Differentiation in Streptomyces coelicolor

“…A DNA fragment containing the rpoZ gene was shown to complement an S. kasugaensis pleiotropic mutant deficient in aerial mycelium formation and kasugamycin biosynthesis. Although sigma factors in Streptomyces have received considerable attention in relation to the expression of antibiotic biosynthetic genes (9,19,20), the role of the RNAP subunit is still obscure.The expression of many genes involved in antibiotic biosynthesis is negatively controlled by the phosphate concentration in the medium (reviewed in references 28 and 30). Limitation of inorganic phosphate produces drastic changes in primary metabolism and triggers the onset of secondary metabolism (34).…”

“…A DNA fragment containing the rpoZ gene was shown to complement an S. kasugaensis pleiotropic mutant deficient in aerial mycelium formation and kasugamycin biosynthesis. Although sigma factors in Streptomyces have received considerable attention in relation to the expression of antibiotic biosynthetic genes (9,19,20), the role of the RNAP subunit is still obscure.…”

The Anti-Anti-Sigma Factor BldG Is Involved in Activation of the Stress Response Sigma Factor σ H in Streptomyces coelicolor A3(2)

“…Four anti-sigma factors have been experimentally verified to interact with and inhibit activity of their partner sigma factors in S. coelicolor. They include UshX (PrsH, SCO5244) for H (46,47,50), RsbA (SCO0599) for B (34), RsmA (SCO7313) for M (14), and RsfA (SCO4677) for F (26) RsfA has also been found to interact with two homologues for anti-anti-sigma factors, SCO0781 and SCO0869 (26). The homologue of anti-antisigma factors, RsbV (SCO7325), has been shown to interact with RsbA and to be involved in activation of B (34).…”