Antonie van Leeuwenhoek

, Volume 78, Issue 3–4, pp 269–276 | Cite as

Effects of increased and deregulated expression of cell division genes on the morphology and on antibiotic production of streptomycetes

  • Gilles P. van Wezel
  • Jannes van der Meulen
  • Elly Taal
  • Henk Koerten
  • Barend Kraal


This paper describes the effects of increased expression of the cell division genes ftsZ, ftsQ, and ssgA on the development of both solid- and liquid-grown mycelium of Streptomyces coelicolor and Streptomyces lividans. Over-expression of ftsZ in S. coelicolor M145 inhibited aerial mycelium formation and blocked sporulation. Such deficient sporulation was also observed for the ftsZ mutant. Over-expression of ftsZ also inhibited morphological differentiation in S. lividans 1326, although aerial mycelium formation was less reduced. Furthermore, antibiotic production was increased in both strains, and in particular the otherwise dormant actinorhodin biosynthesis cluster of S. lividans was activated in liquid- and solid-grown cultures. No significant alterations were observed when the gene dosage of ftsQ was increased. Analysis by transmission electron microscopy of an S. coelicolor strain over-expressing ssgA showed that septum formation had strongly increased in comparison to wild-type S. coelicolor, showing that SsgA clearly influences Streptomyces cell division. The morphology of the hyphae was affected such that irregular septa were produced with a significantly wider diameter, thereby forming spore-like compartments. This suggests that ssgA can induce a process similar to submerged sporulation in Streptomyces strains that otherwise fail to do so. A working model is proposed for the regulation of septum formation and of submerged sporulation.

differentiation FtsZ gene expression septum SsgA transmission electron microscopy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Beall B & Lutkenhaus J (1991) FtsZ in Bacillus subtilis is required for vegetative septation and for asymmetric septation during sporulation. Genes Devel. 5: 447–455Google Scholar
  2. Bibb MJ (1996) The regulation of antibiotic production in Streptomyces coelicolor A3(2). Microbiology 142: 1335–1344Google Scholar
  3. Bibb MJ, White J, Ward JM & Janssen GR (1994) The mRNA for the 23S rRNA methylase encoded by the ermE gene of Saccharopolyspora erythraea is translated in the absence of a conventional ribosome-binding site. Mol. Microbiol. 14: 533–45Google Scholar
  4. Bierman M, Logan R, Obrien K, Seno ET, Rao EN & Schoner BE (1992) Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene 116: 43–49.Google Scholar
  5. Biro S, Bekesi I, Vitalis S & Szabo G (1980) A substance effecting differentiation in Streptomyces griseus. Eur. J. Biochem. 103: 359–363Google Scholar
  6. Biro S, Birko Z & van Wezel GP (2000) Transcriptional and Functional analysis of the gene for Factor C, an extracellular signal protein involved in cytodifferentiation of Streptomyces griseus. Antonie van Leeuwenhoek, this issue.Google Scholar
  7. Birko Z, Sumegi A, Vinnai A, van Wezel GP, Szeszak F, Vitalis S, Szabo PT, Kele Z, Janaki T & Biro S (1999) Characterization of the gene for Factor C, an extracellular signal protein involved in morphological differentiation of Streptomyces griseus. Microbiology 145: 2245–2253Google Scholar
  8. Bramhill D (1997) Bacterial cell division. Annu. Rev. Cell. Dev. Biol. 13: 395–424Google Scholar
  9. Chater KF (1993) Genetics of differentiation in Streptomyces. Annu. Rev. Microbiol. 47: 685–713Google Scholar
  10. Chater KF (1998) Taking a genetic scalpel to the Streptomyces colony. Microbiology 144: 1465–1478.Google Scholar
  11. Chater KF & Losick R (1997) The mycelial life-style of Streptomyces coelicolor A3(2) and its relatives. In: Shapiro JH & Dworkin M (Eds) Bacteria as Multicellular Organisms (pp 149–182). Oxford University Press, New York.Google Scholar
  12. Dai K & Lutkenhaus J (1991) ftsZ is an essential cell division gene in Escherichia coli. J. Bacteriol. 173: 3500–3506Google Scholar
  13. Daza A, Martin JF, Dominguez A & Gil JA (1989) Sporulation of several species of Streptomyces in submerged cultures after nutritional downshift. J. Gen. Microbiol. 135: 2483–2491Google Scholar
  14. Hobbs G, Frazer CM, Gardner DCJ, Flett F & Oliver SG (1989) Dispersed growth of Streptomyces in liquid culture. Appl.Microbiol. Biotechnol. 31: 272–277Google Scholar
  15. Hopwood DA, Bibb MJ, Chater KF, Kieser T, Bruton CJ, Kieser HM, Lydiate DJ, Smith CP, Ward JM & Schrempf H (1985) Genetic manipulation of Streptomyces: a laboratory manual. Norwich: John Innes Foundation.Google Scholar
  16. Janssen GR & Bibb MJ (1993) Derivatives of pUC18 that have BglII sites flanking a modified multiple cloning site and that retain the ability to identify recombinant clones by visual screening of Escherichia coli colonies. Gene 124: 133–134Google Scholar
  17. Kawamoto S & Ensign JC (1995) Cloning and characterization of a gene involved in regulation and sporulation and cell division in Streptomyces griseus. Actinomycetologica 9: 136–151Google Scholar
  18. Kawamoto S, Watanabe H, Hesketh A, Ensign JC & Ochi K (1997) Expression of the ssgA gene product, associated with sporulation and cell division in Streptomyces griseus. Microbiology 143: 1077–1086Google Scholar
  19. Kelemen GH & Buttner MJ (1998) Initiation of aerial mycelium formation in Streptomyces. Curr. Opinion Microbiol. 1: 656–662Google Scholar
  20. Kendrick K & Ensign JC (1983) Sporulation of Streptomyces griseus in submerged culture. J. Bacteriol. 155: 357–366Google Scholar
  21. Larson JL & Herschberger CL (1986) The minimal replicon of a streptomycete plasmid produces an ultrahigh level of plasmid DNA. Plasmid 15: 199–209.Google Scholar
  22. Lutkenhaus J & Addinall SG (1997) Bacterial cell division and the Z ring. Annu. Rev. Biochem. 66: 93–116Google Scholar
  23. Lydiate DJ, Malpartida F & Hopwood DA (1985) The Streptomyces plasmid SCP2*: its functional analysis and development into useful cloning vectors. Gene 35: 223–235Google Scholar
  24. MacNeil DJ, Gewain KM, Ruby CL, Dezeny G, Gibbons PH, & MacNeil T (1992) Analysis of Streptomyces avermitilis genes required for avermectin biosynthesis utilising a novel integration vector. Gene 111: 1–68Google Scholar
  25. Martinez-Costa OH, Martin-Triana AJ, Martinez E, Fernandez-Moreno M & Malpartida F (1999) An additional regulatory gene for actinorhodin production in Streptomyces lividans involves a LysR-type transcription regulator. J. Bacteriol. 181: 4353–4364Google Scholar
  26. McCormick JR, Su EP, Driks A & Losick R (1994) Growth and viability of Streptomyces coelicolor mutant for the cell division gene ftsZ. Mol. Microbiol. 14: 243–254Google Scholar
  27. McCormick JR & Losick R (1996) Cell division gene ftsQ is required for efficient sporulation but not growth and viability in Streptomyces coelicolor A3(2). J. Bacteriol. 178: 5295–5301Google Scholar
  28. Messing J, Crea R & Seeburg PH (1981) A system for shotgun DNA sequencing. Nucleic Acids Res. 9: 309–321Google Scholar
  29. Motamedi H, Shafiee A & Cai SJ (1995) Integrative vectors for heterologous gene expression in Streptomyces spp. Gene 160: 25–31Google Scholar
  30. Sambrook J, Fritsch EF & Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.Google Scholar
  31. Strauch E, Takano E, Baylis HA, & Bibb MJ (1991) The stringent response in Streptomyces coelicolor A3(2). Mol. Microbiol. 5: 289–298Google Scholar
  32. van Wezel GP, van der Meulen J, Kawamoto S, Luiten RGM, Koerten HK & Kraal B (2000) ssgA is essential for sporulation of Streptomyces coelicolor A3(2) and affects hyphal development by stimulating septum formation. J. Bacteriol. 182: 5653–5662Google Scholar
  33. Vara J, Lewandowska-Skarbek M, Wang Y-G, Donadio S & Hutchinson CR (1989) Cloning of genes governing the deoxysugar portion of the erythromycin biosynthesis pathway in saccharopolyspora erythraea (Streptomyces erythreus). J. Bacteriol. 171: 5872–5881Google Scholar
  34. Ward JE Jr & Lutkenhaus J (1985) Overproduction of FtsZ induces minicell formation in E.coli. Cell 42: 941–949Google Scholar
  35. Yanish-Perron C, Vieira J & Messing J (1985) Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13 mp18 and pUC19 vectors.Gene 33: 103–119Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Gilles P. van Wezel
    • 1
  • Jannes van der Meulen
    • 2
  • Elly Taal
    • 3
  • Henk Koerten
    • 2
  • Barend Kraal
    • 3
  1. 1.Department of Biochemistry, Leiden Institute of ChemistryLeiden UniversityRA LeidenThe Netherlands
  2. 2.Center for Electron MicroscopyLeiden University Medical CentreRA LeidenThe Netherlands
  3. 3.Department of Biochemistry, Leiden Institute of ChemistryLeiden UniversityRA LeidenThe Netherlands

Personalised recommendations