1887

Abstract

An homologue () and three -butyrolactone receptor gene homologues (, and ) are coded on the giant linear plasmid pSLA2-L in 7434AN4, a producer of two polyketide antibiotics, lankacidin and lankamycin. Construction of gene disruptants and their phenotypic study revealed that and make a -butyrolactone receptor system in this strain. Addition of a -butyrolactone fraction to an -deficient mutant restored the production of lankacidin and lankamycin, indicating that the SrrX protein is not necessary for this event. In addition to a positive effect on antibiotic production, showed a negative effect on morphological differentiation. The receptor gene reversed both effects of , while the second receptor gene homologue had only a positive function in spore formation. Furthermore, disruption of the third homologue greatly increased the production of lankacidin and lankamycin. Electron microscopic analysis showed that aerial mycelium formation stopped at a different stage in the and mutants. Overall, these results indicated that , , and constitute a complex regulatory system for antibiotic production and morphological differentiation in .

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2006/002170-0
2007-06-01
2020-07-11
Loading full text...

Full text loading...

/deliver/fulltext/micro/153/6/1817.html?itemId=/content/journal/micro/10.1099/mic.0.2006/002170-0&mimeType=html&fmt=ahah

References

  1. Ando N., Matsumori N., Sakuda S., Beppu T., Horinouchi S.. 1997; Involvement of AfsA in A-factor biosynthesis as a key enzyme. J Antibiot (Tokyo)50:847–852[CrossRef]
    [Google Scholar]
  2. Arakawa K., Sugino F., Kodama K., Ishii T., Kinashi H.. 2005; Cyclization mechanism for the synthesis of macrocyclic antibiotic lankacidin in Streptomyces rochei. Chem Biol12:249–256[CrossRef]
    [Google Scholar]
  3. Arakawa K., Kodama K., Tatsuno S., Ide S., Kinashi H.. 2006; Analysis of the loading and hydroxylation steps in lankamycin biosynthesis in Streptomyces rochei. Antimicrob Agents Chemother50:1946–1952[CrossRef]
    [Google Scholar]
  4. Barany F.. 1985; Single-stranded hexameric linkers: a system for in-phase insertion mutagenesis and protein engineering. Gene37:111–123[CrossRef]
    [Google Scholar]
  5. Bentley S. D., Chater K. F., Cerdeno-Tarraga A. M., Challis G. L., Thomson N. R., James K. D., Harris D. E., Quail M. A., Kieser H.. other authors 2002; Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2. Nature417:141–147[CrossRef]
    [Google Scholar]
  6. Bentley S. D., Brown S., Murphy L. D., Harris D. E., Quail M. A., Parkhill J., Barrell B. G., McCormick J. R., Santamaria R. I.. other authors 2004; SCP1, a 356,023 bp linear plasmid adapted to the ecology and developmental biology of its host, Streptomyces coelicolor A3(2. Mol Microbiol51:1615–1628[CrossRef]
    [Google Scholar]
  7. Beyer S., Distler J., Piepersberg W.. 1996; The str gene cluster for the biosynthesis of 5′-hydroxystreptomycin in Streptomyces glaucescens GLA.0 (ETH 22794): new operons and evidence for pathway-specific regulation by StrR. Mol Gen Genet250:775–784
    [Google Scholar]
  8. Bibb M. J.. 2005; Regulation of secondary metabolism in streptomycetes. Curr Opin Microbiol8:208–215[CrossRef]
    [Google Scholar]
  9. Bierman M., Logan R., O'Brien K., Seno E. T., Rao R. N., Schoner B. E.. 1992; Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene116:43–49[CrossRef]
    [Google Scholar]
  10. Chater K. F., Bruton C. J.. 1985; Resistance, regulatory and production genes for the antibiotic methylenomycin are clustered. EMBO J4:1893–1897
    [Google Scholar]
  11. Engel P., Scharfenstein L. L., Dyer J. M., Cary J. W.. 2001; Disruption of a gene encoding a putative gamma-butyrolactone-binding protein in Streptomyces tendae affects nikkomycin production. Appl Microbiol Biotechnol56:414–419[CrossRef]
    [Google Scholar]
  12. Folcher M., Gaillard H., Nguyen L. T., Nguyen K. T., Lacroix P., Bamas-Jacques N., Rinkel M., Thompson C. J.. 2001; Pleiotropic functions of a Streptomyces pristinaespiralis autoregulator receptor in development, antibiotic biosynthesis, and expression of a superoxide dismutase. J Biol Chem276:44297–44306[CrossRef]
    [Google Scholar]
  13. Gravius B., Glocker D., Pigac J., Pandza K., Hranueli D., Cullum J.. 1994; The 387 kb linear plasmid pPZG101 of Streptomyces rimosus and its interactions with the chromosome. Microbiology140:2271–2277[CrossRef]
    [Google Scholar]
  14. Hara O., Beppu T.. 1982; Mutants blocked in streptomycin production in Streptomyces griseus – the role of A-factor. J Antibiot (Tokyo35:349–358[CrossRef]
    [Google Scholar]
  15. Horinouchi S.. 2002; A microbial hormone, A-factor, as a master switch for morphological differentiation and secondary metabolism in Streptomyces griseus. Front Biosci7:d2045d–2057[CrossRef]
    [Google Scholar]
  16. Horinouchi S., Kumada Y., Beppu T.. 1984; Unstable genetic determinant of A-factor biosynthesis in streptomycin-producing organisms: cloning and characterization. J Bacteriol158:481–487
    [Google Scholar]
  17. Ikeda H., Ishikawa J., Hanamoto A., Shinose M., Kikuchi H., Shiba T., Sakaki Y., Hattori M., Omura S.. 2003; Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis. Nat Biotechnol21:526–531[CrossRef]
    [Google Scholar]
  18. Ishikawa J., Niino Y., Hotta K.. 1996; Construction of pRES18 and pRES19, Streptomyces - Escherichia coli shuttle vectors carrying multiple cloning sites. FEMS Microbiol Lett145:113–116[CrossRef]
    [Google Scholar]
  19. Kato J. Y., Suzuki A., Yamazaki H., Ohnishi Y., Horinouchi S.. 2002; Control by A-factor of a metalloendopeptidase gene involved in aerial mycelium formation in Streptomyces griseus. J Bacteriol184:6016–6025[CrossRef]
    [Google Scholar]
  20. Kato J. Y., Miyahisa I., Mashiko M., Ohnishi Y., Horinouchi S.. 2004; A single target is sufficient to account for the biological effects of the A-factor receptor protein of Streptomyces griseus. J Bacteriol186:2206–2211[CrossRef]
    [Google Scholar]
  21. Kawachi R., Akashi T., Kamitani Y., Sy A., Wangchaisoonthorn U., Nihira T., Yamada Y.. 2000; Identification of an AfsA homologue (BarX) from Streptomyces virginiae as a pleiotropic regulator controlling autoregulator biosynthesis, virginiamycin biosynthesis and virginiamycin M1 resistance. Mol Microbiol36:302–313[CrossRef]
    [Google Scholar]
  22. Khokhlov A. S., Anisova L. N., Tovarova I. I., Kleiner E. M., Kovalenko I. V., Krasilnikova O. I., Kornitskaya E. Y., Pliner S. A.. 1973; Effect of A-factor on the growth of asporogenous mutants of Streptomyces griseus , not producing this factor. Z Allg Mikrobiol13:647–655[CrossRef]
    [Google Scholar]
  23. Kieser T., Bibb M. J., Buttner M. J., Chater K. F., Hopwood D. A.. 2000; Practical Streptomyces Genetics Norwich, UK: John Innes Foundation;
    [Google Scholar]
  24. Kinashi H., Shimaji M., Sakai A.. 1987; Giant linear plasmids in Streptomyces which code for antibiotic biosynthesis genes. Nature328:454–456[CrossRef]
    [Google Scholar]
  25. Kinashi H., Mori E., Hatani A., Nimi O.. 1994; Isolation and characterization of large linear plasmids from lankacidin-producing Streptomyces species. J Antibiot (Tokyo47:1447–1455[CrossRef]
    [Google Scholar]
  26. Kinashi H., Fujii S., Hatani A., Kurokawa T., Shinkawa H.. 1998; Physical mapping of the linear plasmid pSLA2-L and localization of the eryAI and actI homologs. Biosci Biotechnol Biochem62:1892–1897[CrossRef]
    [Google Scholar]
  27. Kitani S., Yamada Y., Nihira T.. 2001; Gene replacement analysis of the butyrolactone autoregulator receptor (FarA) reveals that FarA acts as a novel regulator in secondary metabolism of Streptomyces lavendulae FRI-5. J Bacteriol183:4357–4363[CrossRef]
    [Google Scholar]
  28. Lezhava A., Kameoka D., Sugino H., Goshi K., Shinkawa H., Nimi O., Horinouchi S., Beppu T., Kinashi H.. 1997; Chromosomal deletions in Streptomyces griseus that remove the afsA locus. Mol Gen Genet253:478–483[CrossRef]
    [Google Scholar]
  29. Matsuno K., Yamada Y., Lee C. K., Nihira T.. 2004; Identification by gene deletion analysis of barB as a negative regulator controlling an early process of virginiamycin biosynthesis in Streptomyces virginiae. Arch Microbiol181:52–59[CrossRef]
    [Google Scholar]
  30. Miyake K., Kuzuyama T., Horinouchi S., Beppu T.. 1990; The A-factor-binding protein of Streptomyces griseus negatively controls streptomycin production and sporulation. J Bacteriol172:3003–3008
    [Google Scholar]
  31. Mochizuki S., Hiratsu K., Suwa M., Ishii T., Sugino F., Yamada K., Kinashi H.. 2003; The large linear plasmid pSLA2-L of Streptomyces rochei has an unusually condensed gene organization for secondary metabolism. Mol Microbiol48:1501–1510[CrossRef]
    [Google Scholar]
  32. Nakano H., Takehara E., Nihira T., Yamada Y.. 1998; Gene replacement analysis of the Streptomyces virginiae barA gene encoding the butyrolactone autoregulator receptor reveals that BarA acts as a repressor in virginiamycin biosynthesis. J Bacteriol180:3317–3322
    [Google Scholar]
  33. O'Connor T. J., Kanellis P., Nodwell J. 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 Microbiol45:45–57[CrossRef]
    [Google Scholar]
  34. Ohnishi Y., Kameyama S., Onaka H., Horinouchi S.. 1999; The A-factor regulatory cascade leading to streptomycin production in Streptomyces griseus : identification of a target gene of the A-factor receptor. Mol Microbiol34:102–111[CrossRef]
    [Google Scholar]
  35. Ohnishi Y., Yamazaki H., Kato J., Tomono A., Horinouchi S.. 2005; AdpA, a central transcriptional regulator in the A-factor regulatory cascade that leads to morphological development and secondary metabolism in Streptomyces griseus. Biosci Biotechnol Biochem69:431–439[CrossRef]
    [Google Scholar]
  36. Onaka H., Ando N., Nihara T., Yamada Y., Beppu T., Horinouchi S.. 1995; Cloning and characterization of the A-factor receptor gene from Streptomyces griseus. J Bacteriol177:6083–6092
    [Google Scholar]
  37. Onaka H., Nakagawa T., Horinouchi S.. 1998; Involvement of two A-factor receptor homologues in Streptomyces coelicolor A3(2) in the regulation of secondary metabolism and morphogenesis. Mol Microbiol28:743–753
    [Google Scholar]
  38. Pandza S., Biukovic G., Paravic A., Dadbin A., Cullum J., Hranueli D.. 1998; Recombination between the linear plasmid pPZG101 and the linear chromosome of Streptomyces rimosus can lead to exchange of ends. Mol Microbiol28:1165–1176[CrossRef]
    [Google Scholar]
  39. Ramos J. L., Martinez-Bueno M., Molina-Henares A. J., Teran W., Watanabe K., Zhang X., Gallegos M. T., Brennan R., Tobes R.. 2005; The TetR family of transcriptional repressors. Microbiol Mol Biol Rev69:326–356[CrossRef]
    [Google Scholar]
  40. Redenbach M., Ikeda K., Yamasaki M., Kinashi H.. 1998; Cloning and physical mapping of the Eco RI fragments of the giant linear plasmid SCP1. J Bacteriol180:2796–2799
    [Google Scholar]
  41. Sambrook J., Fritsch E. F., Maniatis T.. 1989; Molecular Cloning: a Laboratory Manual , 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  42. Stratigopoulos G., Cundliffe E.. 2002; Expression analysis of the tylosin-biosynthetic gene cluster: pivotal regulatory role of the tylQ product. Chem Biol9:71–78[CrossRef]
    [Google Scholar]
  43. Stratigopoulos G., Gandecha A. R., Cundliffe E.. 2002; Regulation of tylosin production and morphological differentiation in Streptomyces fradiae by TylP, a deduced γ -butyrolactone receptor. Mol Microbiol45:735–744[CrossRef]
    [Google Scholar]
  44. Stratigopoulos G., Bate N., Cundliffe E.. 2004; Positive control of tylosin biosynthesis: pivotal role of TylR. Mol Microbiol54:1326–1334[CrossRef]
    [Google Scholar]
  45. Sugiyama M., Onaka H., Nakagawa T., Horinouchi S.. 1998; Site-directed mutagenesis of the A-factor receptor protein: Val-41 important for DNA-binding and Trp-119 important for ligand-binding. Gene222:133–144[CrossRef]
    [Google Scholar]
  46. Suwa M., Sugino H., Sasaoka A., Mori E., Fujii S., Shinkawa H., Nimi O., Kinashi H.. 2000; Identification of two polyketide synthase gene clusters on the linear plasmid pSLA2-L in Streptomyces rochei. Gene246:123–131[CrossRef]
    [Google Scholar]
  47. Takano E.. 2006; γ -Butyrolactones: Streptomyces signaling molecules regulating antibiotic production and differentiation. Curr Opin Microbiol9:287–294[CrossRef]
    [Google Scholar]
  48. Takano E., Chakaraburtty R., Nihira T., Yamada Y., Bibb M. J.. 2001; A complex role for the γ -butyrolactone SCB1 in regulating antibiotic production in Streptomyces coelicolor A3(2. Mol Microbiol41:1015–1028
    [Google Scholar]
  49. Takano E., Kinoshita H., Mersinias V., Bucca G., Hotchkiss G., Nihira T., Smith C. P., Bibb M., Wohlleben W., Chater K.. 2005; A bacterial hormone (the SCB1) directly controls the expression of a pathway-specific regulatory gene in the cryptic type I polyketide biosynthetic gene cluster of Streptomyces coelicolor. Mol Microbiol56:465–479[CrossRef]
    [Google Scholar]
  50. Wietzorrek A., Bibb M.. 1997; A novel family of proteins that regulates antibiotic production in streptomycetes appears to contain an OmpR-like DNA-binding fold. Mol Microbiol25:1181–1184[CrossRef]
    [Google Scholar]
  51. Yamazaki H., Ohnishi Y., Horinouchi S.. 2000; An A-factor-dependent extracytoplasmic function sigma factor (sigma(AdsA)) that is essential for morphological development in Streptomyces griseus. J Bacteriol182:4596–4605[CrossRef]
    [Google Scholar]
  52. Zhang H., Shinkawa H., Ishikawa J., Kinashi H., Nimi O.. 1997; Improvement of transformation system in Streptomyces using a modified regeneration medium. J Ferment Bioeng83:217–221
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2006/002170-0
Loading
/content/journal/micro/10.1099/mic.0.2006/002170-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error