Streptomyces coelicolor is a Gram-positive soil bacterium that undergoes a complex developmental life cycle. The genome sequence of this organism was recently completed and has revealed the presence of over 60 sigma factors and a multitude of other transcriptional regulators, with a significant number of these being putative two-component signal transduction proteins. The authors have used the criteria established by Hoch and co-workers (Fabret et al., 1999, J Bacteriol 181, 1975–1983) to identify sensor kinase and response regulator genes encoded within the S. coelicolor genome. This analysis has revealed the presence of 84 sensor kinase genes, 67 of which lie adjacent to genes encoding response regulators. This strongly suggests that these paired genes encode two-component systems. In addition there are 13 orphan response regulators encoded in the genome, several of which have already been characterized and are implicated in development and antibiotic production, and 17 unpaired and as yet uncharacterized sensor kinases. This article attempts to infer useful information from sequence analysis and reviews what is currently known about the two-component systems, unpaired sensor kinases and orphan response regulators of S. coelicolor from both published reports and the authors' own unpublished data.
AdamidisT.,
RiggleP.,
ChampnessW.
1990; Mutations in a new Streptomyces coelicolor locus which globally block antibiotic biosynthesis but not sporulation. J Bacteriol 172:2962–2969
AinsaJ. A.,
ParryH. D.,
ChaterK. F.
1999; A response regulator-like protein that functions at an intermediate stage of sporulation in Streptomyces coelicolor A3(2). Mol Microbiol 34:607–619[CrossRef]
BarrettJ. F.,
GoldschmidtR. M.,
LawrenceL. E.
& 19 other authors; 1998; Antibacterial agents that inhibit two-component signal transduction systems. Proc Natl Acad Sci U S A 95:5317–5322[CrossRef]
BentleyS. D.,
ChaterK. F.40 other authorsCerdeno-Tarraga.
2002; Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417:141–147[CrossRef]
Billot-KleinD.,
BlanotD.,
GutmannL.,
van HeijenoortJ.
1997; Association constants for the binding of vancomycin and teicoplanin to N-acetyl-d-alanyl-d-alanine and n-acetyl-d-alanyl-d-serine. Biochem J 304:1021–1022
BishopA.,
FieldingS.,
DysonP.,
HerronP.
2004; Concerted mutagenesis of a streptomycete genome: a link between osmoadaptation and antibiotic production. Genome Res 14:893–900[CrossRef]
BourretR. B.,
HessF.,
SimonM. I.
1990; Conserved aspartate residues and phosphorylation in signal transduction by the chemotaxis protein CheY. Proc Natl Acad Sci U S A 87:41–45[CrossRef]
BrianP.,
RiggleP. J.,
SantosR. A.,
ChampnessW. C.
1996; Global negative regulation of Streptomyces coelicolor antibiotic synthesis mediated by an absA-encoded putative signal transduction system. J Bacteriol 178:3221–3231
ChangH. M.,
ChenM. Y.,
ShiehY. T.,
BibbM. J.,
ChenC. W.
1996; The cutRS signal transduction system of Streptomyces lividans represses the biosynthesis of the polyketide antibiotic actinorhodin. Mol Microbiol 21:1075–1085
ColeS. T.,
BroschR.,
ParkhillJ.39 other authors1998; Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 11:537–544
FabretC.,
HochJ. A.
1998; A two-component signal transduction system essential for growth of Bacillus subtilis: implications for anti-infective therapy. J Bacteriol 180:6375–6383
FabretC.,
FeherV. A.,
HochJ. A.
1999; Two-component signal transduction in Bacillus subtilis: how one organism sees its world. J Bacteriol 181:1975–1983
FinkD.,
WeissschuhN.,
ReutherJ.,
WohllebenW.,
EngelsA.
2002; Two transcriptional regulators GlnR and GlnRII are involved in regulation of nitrogen metabolism in Streptomyces coelicolor A3(2). Mol Microbiol 46:331–347[CrossRef]
FuruyaK.,
HutchinsonC. R.
1996; The DnrR protein of Streptomyces peucetius, a pseudo-response regulator, is a DNA-binding protein involved in the regulation of daunorubicin biosynthesis. J Bacteriol 178:6310–6318
GoughJ.,
KarplusK.,
HugheyR.,
ChothiaC.
2001; Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure. J Mol Biol 313:903–919[CrossRef]
GustB.,
ChallisG. L.,
FowlerK.,
KieserT.,
ChaterK. F.
2003; PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odour geosmin. Proc Natl Acad Sci U S A 100:1541–1546[CrossRef]
GuthrieE. P.,
FlaxmanC. S.,
WhiteJ.,
HodgsonD. A.,
BibbM. J.,
ChaterK. F.
1998; A response-regulator-like activator of antibiotic synthesis from Streptomyces coelicolor A3(2) with an amino-terminal domain that lacks a phosphorylation pocket. Microbiology 144:727–738[CrossRef]
HakenbeckR.,
StockJ. B.
1996; Analysis of two-component signal transduction systems involved in transcriptional regulation. Methods Enzymol 273:281–300
HongH. J.,
PagetM. S. B.,
ButtnerM. J.
2002; A signal transduction system in Streptomyces coelicolor that activates the expression of a putative cell wall glycan operon in response to vancomycin and other cell wall-specific antibiotics. Mol Microbiol 44:1199–1211[CrossRef]
HongH. J.,
HutchingsM. I.,
NeuJ. M.,
WrightG. D.,
PagetM. S. B.,
ButtnerM. J.
2004; Characterisation of an inducible vancomycin resistance system in Streptomyces coelicolor reveals a novel gene (vanK) required for drug resistance. Mol Microbiol 52:1107–1121[CrossRef]
HuangJ.,
LihC. J.,
PanK. H.,
CohenS. N.
2001; Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays. Genes Dev 15:3183–3192[CrossRef]
IshizukaH.,
HorinouchiS.,
KieserH. M.,
HopwoodD. A.,
BeppuT.
1992; A putative two-component regulatory system involved in secondary metabolism in Streptomyces spp.. J Bacteriol 23:7585–7594
JanssenG. R.
1993; Eubacterial, archaebacterial and eukaryotic genes that encode leaderless mRNA. In Industrial Microorganisms: Basic and Applied Molecular Genetics pp. 59–67 Edited by
BaltzR. H.,
HegemanG. D.,
SkatrudP. L.
Washington DC: American Society for Microbiology;
JungK.,
AltendorfK.
2003; Stimulus perception and signal transduction by the KdpD/KdpE system of Escherichia coli. Regulatory Networks in Prokaryotes Edited by
DurreP.,
FriedrichB.
Hethersett, Norwich, UK: Horizon Press;
KeijserB. J. F.,
van WezelG. P.,
CantersG. W.,
VijgenboomE.
2002; Developmental regulation of the Streptomyces lividans ram genes: involvement of RamR in regulation of the ramCSAB operon. J Bacteriol 184:4420–4429[CrossRef]
LevitM.,
LiuY.,
SuretteM.,
StockJ.
1996; Active site interference and asymmetric activation in the chemotaxis protein histidine kinase CheA. J Biol Chem 271:32057–32063[CrossRef]
MartinP. K.,
LiT.,
SunD.,
BiekD. P.,
SchmidM. B.
1999; Role in cell permeability of an essential two-component system in Staphylococcus aureus. J Bacteriol 181:3666–3673
MascherT.,
MargulisN. G.,
WangT.,
YeR. W.,
HelmannJ. D.
2003; Cell wall stress responses in Bacillus subtilis: the regulatory network of the bacitracin stimulon. Mol Microbiol 50:1591–1604[CrossRef]
MolleV.,
ButtnerM. J.
2000; Different alleles of the response regulator gene bldM arrest Streptomyces coelicolor development at distinct stages. Mol Microbiol 36:1265–1278
MooreJ. B.,
ShiauS.-P.,
ReitzerL. J.
1993; Alterations of highly conserved residues in the regulatory domain of nitrogen regulator I (NtrC) of Escherichia coli. J Bacteriol 175:2692–2701
MurzinA. G.,
BrennerS. E.,
HubbardT.,
ChothiaC.
1995; SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol 247:536–540
NguyenK. T.,
WilleyJ. M.,
NguyenL. D.,
NguyenL. T.,
ViollierP. H.,
ThompsonC. J.
2002; A central regulator of morphological differentiation in the multicellular bacterium Streptomyces coelicolor. Mol Microbiol 46:1223–1238[CrossRef]
O'ConnorT. J.,
KanellisP.,
NodwellJ. R.
2002; The ramC gene is required for morphogenesis in Streptomyces coelicolor and expressed in a cell type-specific manner under the direct control of RamR. Mol Microbiol 45:45–57[CrossRef]
OginoT.,
MatsubaraM.,
KatoN.,
NakamuraY.,
MizunoT.
1998; An Escherichia coli protein that exhibits phosphohistidine phosphatase activity towards the HPt domain of the ArcB sensor involved in the multistep His-Asp phosphorelay. Mol Microbiol 27:573–585[CrossRef]
OttenS. L.,
FergusonJ.,
HutchinsonC. R.
1995; Regulation of daunorubicin production in Streptomyces peucetius by the dnrR2 locus. J Bacteriol 177:1216–1224
PagetM. S.,
LeibovitzE.,
ButtnerM. J.
1999; A putative two-component signal transduction system regulates sigma E, a sigma factor required for normal cell wall integrity in Streptomyces coelicolor A3(2). Mol Microbiol 33:97–107[CrossRef]
PeregoM.
2001; A new family of aspartyl phosphate phosphatases targeting the sporulation transcription factor Spo0A of Bacillus subtilis. Mol Microbiol 42:133–143
PerezE.,
SamperS.,
BordasY.,
GuilhotC.,
GicquelB.,
MartinC.
2001; An essential role for phoP in Mycobacterium tuberculosis virulence. Mol Microbiol 41:179–187[CrossRef]
PootoolalJ.,
ThomasM. G.,
MarshallC. G.,
NeuJ. M.,
HubbardB. K.,
WalshC. T.,
WrightG. D.
2002; Assembling the glycopeptide antibiotic scaffold: the biosynthesis of A47934 from Streptomyces toyocaensis NRRL15009. Proc Natl Acad Sci U S A 25:8962–8967
ReyratJ.-M.,
DavidM.,
BatutJ.,
BoistardP.
1994; FixL of Rhizobium meliloti enhances the transcriptional activity of a mutant FixJD54N protein by phosphorylation on an alternative residue. J Bacteriol 176:1969–1976
RohrerS.,
Berger-BachiB.
2003; FemABX peptidyl transferases: a link between branched-chain cell wall peptide formation and beta-lactam resistance in gram-positive cocci. Antimicrob Agents Chemother 47:837–846[CrossRef]
ShiL.,
HulettF. M.
1999; The cytoplasmic kinase domain of PhoR is sufficient for the low phosphate-inducible expression of pho regulon genes in Bacillus subtilis. Mol Microbiol 31:211–222[CrossRef]
Sola-LandaA.,
MouraR. S.,
MartinJ. F.
2003; The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans. Proc Natl Acad Sci U S A 100:6133–6138[CrossRef]
SteynA. J.,
JosephJ.,
BloomB. R.
2003; Interaction of the sensor module of Mycobacterium tuberculosis H37Rv KdpD with members of the Lpr family. Mol Microbiol 47:1075–1089[CrossRef]
StoverC. K.,
PhamX. Q.,
ErwinA. L.
& 28 other authors; 2000; Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406:959–964[CrossRef]
TaoW.,
MaloneC. L.,
AultA. D.,
DeschenesR. J.,
FasslerJ. S.
2002; A cytoplasmic coiled-coil domain is required for histidine kinase activity of the yeast osmosensor, SLN1. Mol Microbiol 43:459–473[CrossRef]
TsujiboH.,
HatanoN.,
OkamotoT.,
EndoH.,
MiyamotoK.,
InamoriY.
1999; Synthesis of chitinase in Streptomyces thermoviolaceus is regulated by a two-component sensor-regulator system. FEMS Microbiol Lett 181:83–90[CrossRef]
UedaK.,
HshehC.-W.,
TosakiH.,
ShinkawaH.,
BeppuT.,
HorinouchiS.
1993; A gene cluster involved in aerial mycelium formation in Streptomyces griseus encodes proteins similar to response regulators of two-component regulatory systems and membrane translocators. J Bacteriol 175:2006–2016
WangL.,
GrauR.,
PeregoM.,
HochJ. A.
1997; A novel histidine kinase inhibitor regulating development in Bacillus subtilis. Genes Dev 11:2569–2579[CrossRef]
WrayL. V.,
FisherS. H.
1991; Identification and cloning of the glnR locus, which is required for transcription of theglnA gene in Streptomyces coelicolor. J Bacteriol 173:7351–7360
ZhouL.,
LeiX. H.,
BochnerB. R.,
WannerB. L.
2003; Phenotype microarray analysis of Escherichia coli K-12 mutants with deletions of all two-component systems. J Bacteriol 185:4956–4972[CrossRef]
ZhulinI. B.,
TaylorB. L.,
DixonR.
1997; PAS domain S-boxes in archaea, bacteria and sensors for oxygen and redox. Trends Biochem Sci 22:331–333[CrossRef]