Regulation of the Biosynthesis of the Macrolide Antibiotic Spiramycin in Streptomyces ambofaciens
10.1128/jb.00712-10
Crossref journal-article
American Society for Microbiology
Journal of Bacteriology (235)
Abstract

ABSTRACT Streptomyces ambofaciens synthesizes the macrolide antibiotic spiramycin. The biosynthetic gene cluster for spiramycin has been characterized for S. ambofaciens. In addition to the regulatory gene srmR ( srm22 ), previously identified (M. Geistlich et al., Mol. Microbiol. 6:2019-2029, 1992), three putative regulatory genes had been identified by sequence analysis. Gene expression analysis and gene inactivation experiments showed that only one of these three genes, srm40 , plays a major role in the regulation of spiramycin biosynthesis. The disruption of srm22 or srm40 eliminated spiramycin production while their overexpression increased spiramycin production. Expression analysis was performed by reverse transcription-PCR (RT-PCR) for all the genes of the cluster in the wild-type strain and in the srm22 ( srmR ) and srm40 deletion mutants. The results from the expression analysis, together with the ones from the complementation experiments, indicated that Srm22 is required for srm40 expression, Srm40 being a pathway-specific activator that controls most, if not all, of the spiramycin biosynthetic genes.

Bibliography

Karray, F., Darbon, E., Nguyen, H. C., Gagnat, J., & Pernodet, J.-L. (2010). Regulation of the Biosynthesis of the Macrolide Antibiotic Spiramycin in Streptomyces ambofaciens. Journal of Bacteriology, 192(21), 5813–5821.

Authors 5
  1. Fatma Karray (first)
  2. Emmanuelle Darbon (additional)
  3. Hoang Chuong Nguyen (additional)
  4. Josette Gagnat (additional)
  5. Jean-Luc Pernodet (additional)
References 49 Referenced 30
  1. 10.1128/jb.172.6.2962-2969.1990
  2. 10.1128/JB.187.7.2491-2500.2005
  3. Arisawa, A., N. Kawamura, H. Tsunekawa, K. Okamura, H. Tone, and R. Okamoto. 1993. Cloning and nucleotide sequences of two genes involved in the 4″-O-acylation of macrolide antibiotics from Streptomyces thermotolerans. Biosci. Biotechnol. Biochem. 57 : 2020-2025. (10.1271/bbb.57.2020) / Biosci. Biotechnol. Biochem. (1993)
  4. Bate, N., A. R. Butler, A. R. Gandecha, and E. Cundliffe. 1999. Multiple regulatory genes in the tylosin biosynthetic cluster of Streptomyces fradiae. Chem. Biol. 6 : 617-624. (10.1016/S1074-5521(99)80113-6) / Chem. Biol. (1999)
  5. Bibb, M. J. 2005. Regulation of secondary metabolism in streptomycetes. Curr. Opin. Microbiol. 8 : 208-215. (10.1016/j.mib.2005.02.016) / Curr. Opin. Microbiol. (2005)
  6. Bierman, M., R. Logan, K. O'Brien, E. T. Seno, R. N. Rao, and B. E. Schoner. 1992. Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene 116 : 43-49. (10.1016/0378-1119(92)90627-2) / Gene (1992)
  7. Blondelet-Rouault, M. H., J. Weiser, A. Lebrihi, P. Branny, and J. L. Pernodet. 1997. Antibiotic resistance gene cassettes derived from the omega interposon for use in E. coli and Streptomyces. Gene 190 : 315-317. (10.1016/S0378-1119(97)00014-0) / Gene (1997)
  8. Brown, E. D. 2005. Conserved P-loop GTPases of unknown function in bacteria: an emerging and vital ensemble in bacterial physiology. Biochem. Cell Biol. 83 : 738-746. (10.1139/o05-162) / Biochem. Cell Biol. (2005)
  9. 10.1128/JB.01989-07
  10. Platenolide synthase gene. 1999
  11. 10.1128/jb.172.6.3367-3378.1990
  12. Chater, K. F., and G. Chandra. 2008. The use of the rare UUA codon to define “expression space” for genes involved in secondary metabolism, development and environmental adaptation in streptomyces. J. Microbiol. 46 : 1-11. (10.1007/s12275-007-0233-1) / J. Microbiol. (2008)
  13. Chaveroche, M. K., J. M. Ghigo, and C. d'Enfert. 2000. A rapid method for efficient gene replacement in the filamentous fungus Aspergillus nidulans. Nucleic Acids Res. 28 : E97. (10.1093/nar/28.22.e97) / Nucleic Acids Res. (2000)
  14. Chng, C., A. M. Lum, J. A. Vroom, and C. M. Kao. 2008. A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea. Proc. Natl. Acad. Sci. U. S. A. 105 : 11346-11351. (10.1073/pnas.0803622105) / Proc. Natl. Acad. Sci. U. S. A. (2008)
  15. Cundliffe, E. 2008. Control of tylosin biosynthesis in Streptomyces fradiae. J. Microbiol. Biotechnol. 18 : 1485-1491. / J. Microbiol. Biotechnol. (2008)
  16. Cundliffe, E., N. Bate, A. Butler, S. Fish, A. Gandecha, and L. Merson-Davies. 2001. The tylosin-biosynthetic genes of Streptomyces fradiae. Antonie Van Leeuwenhoek 79 : 229-234. (10.1023/A:1012065300116) / Antonie Van Leeuwenhoek (2001)
  17. 10.1128/AEM.69.3.1647-1654.2003
  18. De Schrijver, A., and R. De Mot. 1999. A subfamily of MalT-related ATP-dependent regulators in the LuxR family. Microbiology 145(6): 1287-1288. (10.1099/13500872-145-6-1287) / Microbiology (1999)
  19. Doumith, M., P. Weingarten, U. F. Wehmeier, K. Salah-Bey, B. Benhamou, C. Capdevila, J. M. Michel, W. Piepersberg, and M. C. Raynal. 2000. Analysis of genes involved in 6-deoxyhexose biosynthesis and transfer in Saccharopolyspora erythraea. Mol. Gen. Genet. 264 : 477-485. (10.1007/s004380000329) / Mol. Gen. Genet. (2000)
  20. Geistlich, M., R. Losick, J. R. Turner, and R. N. Rao. 1992. Characterization of a novel regulatory gene governing the expression of a polyketide synthase gene in Streptomyces ambofaciens. Mol. Microbiol. 6 : 2019-2029. (10.1111/j.1365-2958.1992.tb01374.x) / Mol. Microbiol. (1992)
  21. 10.1128/AAC.42.10.2612
  22. Gust, B., G. L. Challis, K. Fowler, T. Kieser, and K. F. Chater. 2003. PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc. Natl. Acad. Sci. U. S. A. 100 : 1541-1546. (10.1073/pnas.0337542100) / Proc. Natl. Acad. Sci. U. S. A. (2003)
  23. Guthrie, E. P., C. S. Flaxman, J. White, D. A. Hodgson, M. J. Bibb, and K. F. Chater. 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. (10.1099/00221287-144-3-727) / Microbiology (1998)
  24. Hesketh, A., W. J. Chen, J. Ryding, S. Chang, and M. Bibb. 2007. The global role of ppGpp synthesis in morphological differentiation and antibiotic production in Streptomyces coelicolor A3(2). Genome Biol. 8 : R161. (10.1186/gb-2007-8-8-r161) / Genome Biol. (2007)
  25. Karray, F., E. Darbon, N. Oestreicher, H. Dominguez, K. Tuphile, J. Gagnat, M. H. Blondelet-Rouault, C. Gerbaud, and J. L. Pernodet. 2007. Organization of the biosynthetic gene cluster for the macrolide antibiotic spiramycin in Streptomyces ambofaciens. Microbiology 153 : 4111-4122. (10.1099/mic.0.2007/009746-0) / Microbiology (2007)
  26. Khanin, R., V. Vinciotti, V. Mersinias, C. P. Smith, and E. Wit. 2007. Statistical reconstruction of transcription factor activity using Michaelis-Menten kinetics. Biometrics 63 : 816-823. (10.1111/j.1541-0420.2007.00757.x) / Biometrics (2007)
  27. Practical Streptomyces genetics. 2000
  28. Kuhstoss, S., M. Huber, J. R. Turner, J. W. Paschal, and R. N. Rao. 1996. Production of a novel polyketide through the construction of a hybrid polyketide synthase. Gene 183 : 231-236. (10.1016/S0378-1119(96)00565-3) / Gene (1996)
  29. 10.1128/JB.00305-07
  30. Miller, V. L., and J. J. Mekalanos. 1988. A novel suicide vector and its use in construction of insertion mutations: osmoregulation of outer membrane proteins and virulence determinants in Vibrio cholerae requires toxR. J. Bacteriol. 170 : 2575-2583. (10.1128/JB.170.6.2575-2583.1988) / J. Bacteriol. (1988)
  31. Nakano, Y., Y. Yoshida, Y. Yamashita, and T. Koga. 1995. Construction of a series of pACYC-derived plasmid vectors. Gene 162 : 157-158. (10.1016/0378-1119(95)00320-6) / Gene (1995)
  32. 10.1128/AAC.01602-09
  33. 10.1128/jb.179.1.122-127.1997
  34. Pernodet, J. L., M. T. Alegre, M. H. Blondelet-Rouault, and M. Guerineau. 1993. Resistance to spiramycin in Streptomyces ambofaciens, the producer organism, involves at least two different mechanisms. J. Gen. Microbiol. 139 : 1003-1011. (10.1099/00221287-139-5-1003) / J. Gen. Microbiol. (1993)
  35. Pinnert-Sindico, S. 1954. Une nouvelle espèce de Streptomyces productrice d'antibiotiques: Streptomyces ambofaciens n. sp. Ann. Inst. Pasteur (Paris) 87 : 702-707. / Ann. Inst. Pasteur (Paris) (1954)
  36. 10.1128/AEM.00167-06
  37. Rigali, S., A. Derouaux, F. Giannotta, and J. Dusart. 2002. Subdivision of the helix-turn-helix GntR family of bacterial regulators in the FadR, HutC, MocR, and YtrA subfamilies. J. Biol. Chem. 277 : 12507-12515. (10.1074/jbc.M110968200) / J. Biol. Chem. (2002)
  38. Rigali, S., H. Nothaft, E. E. Noens, M. Schlicht, S. Colson, M. Muller, B. Joris, H. K. Koerten, D. A. Hopwood, F. Titgemeyer, and G. P. van Wezel. 2006. The sugar phosphotransferase system of Streptomyces coelicolor is regulated by the GntR-family regulator DasR and links N-acetylglucosamine metabolism to the control of development. Mol. Microbiol. 61 : 1237-1251. (10.1111/j.1365-2958.2006.05319.x) / Mol. Microbiol. (2006)
  39. Rigali, S., F. Titgemeyer, S. Barends, S. Mulder, A. W. Thomae, D. A. Hopwood, and G. P. van Wezel. 2008. Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces. EMBO Rep. 9 : 670-675. (10.1038/embor.2008.83) / EMBO Rep. (2008)
  40. Molecular cloning: a laboratory manual 2001
  41. Simon, R., U. Priefer, and A. Puhler. 1983. A broad host range mobilization system for in vivo genetic engineering: transposon mutagenesis in gram negative bacteria. Biotechnology (NY) 1 : 784-791. (10.1038/nbt1183-784) / Biotechnology (NY) (1983)
  42. Stratigopoulos, G., N. Bate, and E. Cundliffe. 2004. Positive control of tylosin biosynthesis: pivotal role of TylR. Mol. Microbiol. 54 : 1326-1334. (10.1111/j.1365-2958.2004.04347.x) / Mol. Microbiol. (2004)
  43. Stratigopoulos, G., and E. Cundliffe. 2002. Inactivation of a transcriptional repressor during empirical improvement of the tylosin producer, Streptomyces fradiae. J. Ind. Microbiol. Biotechnol. 28 : 219-224. (10.1038/sj.jim.7000234) / J. Ind. Microbiol. Biotechnol. (2002)
  44. Takano, E. 2006. Gamma-butyrolactones: Streptomyces signalling molecules regulating antibiotic production and differentiation. Curr. Opin. Microbiol. 9 : 287-294. (10.1016/j.mib.2006.04.003) / Curr. Opin. Microbiol. (2006)
  45. 10.1128/jb.179.3.627-633.1997
  46. Wietzorrek, A., and M. Bibb. 1997. A novel family of proteins that regulates antibiotic production in streptomycetes appears to contain an OmpR-like DNA-binding fold. Mol. Microbiol. 25 : 1181-1184. (10.1046/j.1365-2958.1997.5421903.x) / Mol. Microbiol. (1997)
  47. 10.1128/JB.183.11.3468-3475.2001
  48. Yu, D., H. M. Ellis, E. C. Lee, N. A. Jenkins, N. G. Copeland, and D. L. Court. 2000. An efficient recombination system for chromosome engineering in Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 97 : 5978-5983. (10.1073/pnas.100127597) / Proc. Natl. Acad. Sci. U. S. A. (2000)
  49. Zhang, Y. X., K. Perry, V. A. Vinci, K. Powell, W. P. Stemmer, and S. B. del Cardayre. 2002. Genome shuffling leads to rapid phenotypic improvement in bacteria. Nature 415 : 644-646. (10.1038/415644a) / Nature (2002)
Dates
Type When
Created 14 years, 11 months ago (Sept. 3, 2010, 10:13 p.m.)
Deposited 4 years ago (July 29, 2021, 1:14 p.m.)
Indexed 3 weeks ago (Aug. 7, 2025, 4:58 a.m.)
Issued 14 years, 9 months ago (Nov. 1, 2010)
Published 14 years, 9 months ago (Nov. 1, 2010)
Published Print 14 years, 9 months ago (Nov. 1, 2010)
Funders 0

None

@article{Karray_2010, title={Regulation of the Biosynthesis of the Macrolide Antibiotic Spiramycin in Streptomyces ambofaciens}, volume={192}, ISSN={1098-5530}, url={http://dx.doi.org/10.1128/jb.00712-10}, DOI={10.1128/jb.00712-10}, number={21}, journal={Journal of Bacteriology}, publisher={American Society for Microbiology}, author={Karray, Fatma and Darbon, Emmanuelle and Nguyen, Hoang Chuong and Gagnat, Josette and Pernodet, Jean-Luc}, year={2010}, month=nov, pages={5813–5821} }