Logo of jbacterPermissionsJournals.ASM.orgJournalJB ArticleJournal InfoAuthorsReviewers
J Bacteriol. Sep 1997; 179(18): 5854–5861.
PMCID: PMC179477

The ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2) plays a conditional role in antibiotic production and morphological differentiation.


Deletion of most of the coding region of the ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2) resulted in loss of ppGpp synthesis, both upon entry into stationary phase under conditions of nitrogen limitation and following amino acid starvation during exponential growth, but had no effect on growth rate. The relA mutant, which showed continued rRNA synthesis upon amino acid depletion (the relaxed response), failed to produce the antibiotics undecylprodigiosin (Red) and actinorhodin (Act) under conditions of nitrogen limitation. The latter appears to reflect diminished transcription of pathway-specific regulatory genes for Red and Act production, redD and actII-ORF4, respectively. In addition to the changes in secondary metabolism, the relA mutant showed a marked delay in the onset and extent of morphological differentiation, resulting in a conspicuously altered colony morphology.

Full Text

The Full Text of this article is available as a PDF (1.1M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bartlett MS, Gourse RL. Growth rate-dependent control of the rrnB P1 core promoter in Escherichia coli. J Bacteriol. 1994 Sep;176(17):5560–5564. [PMC free article] [PubMed]
  • Baylis HA, Bibb MJ. Organisation of the ribosomal RNA genes in Streptomyces coelicolor A3(2). Mol Gen Genet. 1988 Feb;211(2):191–196. [PubMed]
  • Baylis HA, Bibb MJ. Transcriptional analysis of the 16S rRNA gene of the rrnD gene set of Streptomyces coelicolor A3(2). Mol Microbiol. 1988 Sep;2(5):569–579. [PubMed]
  • Bedford DJ, Laity C, Buttner MJ. Two genes involved in the phase-variable phi C31 resistance mechanism of Streptomyces coelicolor A3(2). J Bacteriol. 1995 Aug;177(16):4681–4689. [PMC free article] [PubMed]
  • Bennett PM, Grinsted J, Richmond MH. Transposition of TnA does not generate deletions. Mol Gen Genet. 1977 Jul 20;154(2):205–211. [PubMed]
  • Bierman M, Logan R, O'Brien K, Seno ET, Rao RN, Schoner BE. Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene. 1992 Jul 1;116(1):43–49. [PubMed]
  • Bystrykh LV, Fernández-Moreno MA, Herrema JK, Malpartida F, Hopwood DA, Dijkhuizen L. Production of actinorhodin-related "blue pigments" by Streptomyces coelicolor A3(2). J Bacteriol. 1996 Apr;178(8):2238–2244. [PMC free article] [PubMed]
  • Chakraburtty R, White J, Takano E, Bibb M. Cloning, characterization and disruption of a (p)ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2). Mol Microbiol. 1996 Jan;19(2):357–368. [PubMed]
  • Chater KF, Bruton CJ, King AA, Suarez JE. The expression of Streptomyces and Escherichia coli drug-resistance determinants cloned into the Streptomyces phage phi C31. Gene. 1982 Jul-Aug;19(1):21–32. [PubMed]
  • Condon C, French S, Squires C, Squires CL. Depletion of functional ribosomal RNA operons in Escherichia coli causes increased expression of the remaining intact copies. EMBO J. 1993 Nov;12(11):4305–4315. [PMC free article] [PubMed]
  • Davis NK, Chater KF. Spore colour in Streptomyces coelicolor A3(2) involves the developmentally regulated synthesis of a compound biosynthetically related to polyketide antibiotics. Mol Microbiol. 1990 Oct;4(10):1679–1691. [PubMed]
  • Fernández-Moreno MA, Caballero JL, Hopwood DA, Malpartida F. The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of Streptomyces. Cell. 1991 Aug 23;66(4):769–780. [PubMed]
  • Fiil N, Friesen JD. Isolation of "relaxed" mutants of Escherichia coli. J Bacteriol. 1968 Feb;95(2):729–731. [PMC free article] [PubMed]
  • Floriano B, Bibb M. afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3(2). Mol Microbiol. 1996 Jul;21(2):385–396. [PubMed]
  • Gaal T, Gourse RL. Guanosine 3'-diphosphate 5'-diphosphate is not required for growth rate-dependent control of rRNA synthesis in Escherichia coli. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5533–5537. [PMC free article] [PubMed]
  • Gallant JA. Stringent control in E. coli. Annu Rev Genet. 1979;13:393–415. [PubMed]
  • Gentry DR, Hernandez VJ, Nguyen LH, Jensen DB, Cashel M. Synthesis of the stationary-phase sigma factor sigma s is positively regulated by ppGpp. J Bacteriol. 1993 Dec;175(24):7982–7989. [PMC free article] [PubMed]
  • Gramajo HC, Takano E, Bibb MJ. Stationary-phase production of the antibiotic actinorhodin in Streptomyces coelicolor A3(2) is transcriptionally regulated. Mol Microbiol. 1993 Mar;7(6):837–845. [PubMed]
  • Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. [PubMed]
  • Hernandez VJ, Bremer H. Guanosine tetraphosphate (ppGpp) dependence of the growth rate control of rrnB P1 promoter activity in Escherichia coli. J Biol Chem. 1990 Jul 15;265(20):11605–11614. [PubMed]
  • Hernandez VJ, Bremer H. Escherichia coli ppGpp synthetase II activity requires spoT. J Biol Chem. 1991 Mar 25;266(9):5991–5999. [PubMed]
  • Hernandez VJ, Bremer H. Characterization of RNA and DNA synthesis in Escherichia coli strains devoid of ppGpp. J Biol Chem. 1993 May 25;268(15):10851–10862. [PubMed]
  • Hopwood DA, Chater KF, Bibb MJ. Genetics of antibiotic production in Streptomyces coelicolor A3(2), a model streptomycete. Biotechnology. 1995;28:65–102. [PubMed]
  • Jones GH, Bibb MJ. Guanosine pentaphosphate synthetase from Streptomyces antibioticus is also a polynucleotide phosphorylase. J Bacteriol. 1996 Jul;178(14):4281–4288. [PMC free article] [PubMed]
  • Jones GH, Paget MS, Chamberlin L, Buttner MJ. Sigma-E is required for the production of the antibiotic actinomycin in Streptomyces antibioticus. Mol Microbiol. 1997 Jan;23(1):169–178. [PubMed]
  • Kieser HM, Kieser T, Hopwood DA. A combined genetic and physical map of the Streptomyces coelicolor A3(2) chromosome. J Bacteriol. 1992 Sep;174(17):5496–5507. [PMC free article] [PubMed]
  • Kuhstoss S, Rao RN. Analysis of the integration function of the streptomycete bacteriophage phi C31. J Mol Biol. 1991 Dec 20;222(4):897–908. [PubMed]
  • MacNeil DJ, Occi JL, Gewain KM, MacNeil T, Gibbons PH, Ruby CL, Danis SJ. Complex organization of the Streptomyces avermitilis genes encoding the avermectin polyketide synthase. Gene. 1992 Jun 15;115(1-2):119–125. [PubMed]
  • Malpartida F, Hopwood DA. Physical and genetic characterisation of the gene cluster for the antibiotic actinorhodin in Streptomyces coelicolor A3(2). Mol Gen Genet. 1986 Oct;205(1):66–73. [PubMed]
  • Martínez-Costa OH, Arias P, Romero NM, Parro V, Mellado RP, Malpartida F. A relA/spoT homologous gene from Streptomyces coelicolor A3(2) controls antibiotic biosynthetic genes. J Biol Chem. 1996 May 3;271(18):10627–10634. [PubMed]
  • Mazodier P, Petter R, Thompson C. Intergeneric conjugation between Escherichia coli and Streptomyces species. J Bacteriol. 1989 Jun;171(6):3583–3585. [PMC free article] [PubMed]
  • Metzger S, Sarubbi E, Glaser G, Cashel M. Protein sequences encoded by the relA and the spoT genes of Escherichia coli are interrelated. J Biol Chem. 1989 Jun 5;264(16):9122–9125. [PubMed]
  • Ochi K. Occurrence of the stringent response in Streptomyces sp. and its significance for the initiation of morphological and physiological differentiation. J Gen Microbiol. 1986 Sep;132(9):2621–2631. [PubMed]
  • Ochi K. Metabolic initiation of differentiation and secondary metabolism by Streptomyces griseus: significance of the stringent response (ppGpp) and GTP content in relation to A factor. J Bacteriol. 1987 Aug;169(8):3608–3616. [PMC free article] [PubMed]
  • Ochi K. Streptomyces relC mutants with an altered ribosomal protein ST-L11 and genetic analysis of a Streptomyces griseus relC mutant. J Bacteriol. 1990 Jul;172(7):4008–4016. [PMC free article] [PubMed]
  • Ochi K. A relaxed (rel) mutant of Streptomyces coelicolor A3(2) with a missing ribosomal protein lacks the ability to accumulate ppGpp, A-factor and prodigiosin. J Gen Microbiol. 1990 Dec;136(12):2405–2412. [PubMed]
  • Oh SH, Chater KF. Denaturation of circular or linear DNA facilitates targeted integrative transformation of Streptomyces coelicolor A3(2): possible relevance to other organisms. J Bacteriol. 1997 Jan;179(1):122–127. [PMC free article] [PubMed]
  • Sarubbi E, Rudd KE, Cashel M. Basal ppGpp level adjustment shown by new spoT mutants affect steady state growth rates and rrnA ribosomal promoter regulation in Escherichia coli. Mol Gen Genet. 1988 Aug;213(2-3):214–222. [PubMed]
  • Schreiber G, Metzger S, Aizenman E, Roza S, Cashel M, Glaser G. Overexpression of the relA gene in Escherichia coli. J Biol Chem. 1991 Feb 25;266(6):3760–3767. [PubMed]
  • Singer M, Kaiser D. Ectopic production of guanosine penta- and tetraphosphate can initiate early developmental gene expression in Myxococcus xanthus. Genes Dev. 1995 Jul 1;9(13):1633–1644. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Strauch E, Takano E, Baylis HA, Bibb MJ. The stringent response in Streptomyces coelicolor A3(2). Mol Microbiol. 1991 Feb;5(2):289–298. [PubMed]
  • Takano E, Gramajo HC, Strauch E, Andres N, White J, Bibb MJ. Transcriptional regulation of the redD transcriptional activator gene accounts for growth-phase-dependent production of the antibiotic undecylprodigiosin in Streptomyces coelicolor A3(2). Mol Microbiol. 1992 Oct;6(19):2797–2804. [PubMed]
  • White J, Bibb M. bldA dependence of undecylprodigiosin production in Streptomyces coelicolor A3(2) involves a pathway-specific regulatory cascade. J Bacteriol. 1997 Feb;179(3):627–633. [PMC free article] [PubMed]
  • Xiao H, Kalman M, Ikehara K, Zemel S, Glaser G, Cashel M. Residual guanosine 3',5'-bispyrophosphate synthetic activity of relA null mutants can be eliminated by spoT null mutations. J Biol Chem. 1991 Mar 25;266(9):5980–5990. [PubMed]
  • Zalacain M, González A, Guerrero MC, Mattaliano RJ, Malpartida F, Jiménez A. Nucleotide sequence of the hygromycin B phosphotransferase gene from Streptomyces hygroscopicus. Nucleic Acids Res. 1986 Feb 25;14(4):1565–1581. [PMC free article] [PubMed]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)


Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links
  • Taxonomy
    Related taxonomy entry
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...