1887

Abstract

The prodigiosin biosynthesis gene cluster ( cluster) from two strains of ( ATCC 274 and sp. ATCC 39006) has been cloned, sequenced and expressed in heterologous hosts. Sequence analysis of the respective clusters revealed 14 ORFs in ATCC 274 and 15 ORFs in sp. ATCC 39006. In each species, predicted gene products showed similarity to polyketide synthases (PKSs), non-ribosomal peptide synthases (NRPSs) and the Red proteins of A3(2). Comparisons between the two clusters and the cluster from A3(2) revealed some important differences. A modified scheme for the biosynthesis of prodigiosin, based on the pathway recently suggested for the synthesis of undecylprodigiosin, is proposed. The distribution of the cluster within several sp. isolates is demonstrated and the presence of cryptic clusters in some strains shown. The cluster of ATCC 274 is flanked by and homologues and this configuration is demonstrated in several strains, whilst these genes are contiguous in strains lacking the cluster.

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2004-11-01
2024-12-08
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References

  1. Alexeev D., Alexeeva M., Baxter R. L., Campopiano D. J., Webster S. P., Sawyer L. 1998; The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme. J Mol Biol 284:401–419 [CrossRef]
    [Google Scholar]
  2. Amábile-Cuevas C. F., Demple B. 1991; Molecular characterization of the soxRS genes of Escherichia coli: two genes control a superoxide stress regulon. Nucleic Acids Res 19:4479–4484 [CrossRef]
    [Google Scholar]
  3. Aucken H. M., Pitt T. L. 1998; Antibiotic resistance and putative virulence factors of Serratia marcescens with respect to O and K serotypes. J Med Microbiol 47:1105–1113 [CrossRef]
    [Google Scholar]
  4. Blazevic D. J. 1970 The Genus Serratia Boca, Raton, FL: CRC Press Inc;
    [Google Scholar]
  5. Braun V., Schmitz G. 1980; Excretion of a protease by Serratia marcescens. Arch Microbiol 124:55–61 [CrossRef]
    [Google Scholar]
  6. Brocklehurst K. R., Hobman J. L., Lawley B., Blank L., Marshall S. J., Brown N. L., Morby A. P. 1999; ZntR is a Zn(II)-responsive MerR-like transcriptional regulator of zntA in Escherichia coli . Mol Microbiol 31:893–902 [CrossRef]
    [Google Scholar]
  7. Bycroft B. W., Maslen C., Box S. J., Brown A., Tyler J. W. 1987; The isolation and characterisation of (3R,5R)- and (3S,5R)-carbapenem-3-carboxylic acid from Serratia and Erwinia species and their putative biosynthetic role. J Chem Soc Chem Commun 21:1623–1625
    [Google Scholar]
  8. Cámpas C., Dalmau M., Montaner B., Barragan M., Bellosillo B., Colomer D., Pons G., Perez-Tomas R., Gil J. 2003; Prodigiosin induces apoptosis of B and T cells from B-cell chronic lymphocytic leukemia. Leukemia 17:746–750 [CrossRef]
    [Google Scholar]
  9. Carbonell G. V., Della Colleta H. H., Yano T., Darini A. L., Levy C. E., Fonseca B. A. 2000; Clinical relevance and virulence factors of pigmented Serratia marcescens. FEMS Immunol Med Microbiol 28:143–149 [CrossRef]
    [Google Scholar]
  10. Cerdeño A. M., Bibb M. J., Challis G. L. 2001; Analysis of the prodiginine biosynthesis gene cluster of Streptomyces coelicolor A3(2): new mechanisms for chain initiation and termination in modular multienzymes. Chem Biol 8:817–829 [CrossRef]
    [Google Scholar]
  11. Changela A., Chen K., Xue Y., Holschen J., Outten C. E., O'Halloran T. V., Mondragon A. 2003; Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR. Science 301:1383–1387 [CrossRef]
    [Google Scholar]
  12. Chiu M. L., Folcher M., Katoh T., Puglia A. M., Vohradsky J., Yun B. S., Seto H., Thompson C. J. 1999; Broad spectrum thiopeptide recognition specificity of the Streptomyces lividans TipAL protein and its role in regulating gene expression. J Biol Chem 274:20578–20586 [CrossRef]
    [Google Scholar]
  13. Clegg S., Allen B. L. 1985; Molecular cloning and expression of an extracellular nuclease of Serratia marcescens in Escherchia coli . FEMS Microbiol Lett 27:257–262 [CrossRef]
    [Google Scholar]
  14. Coco E. A., Narva K. E., Feitelson J. S. 1991; New classes of Streptomyces coelicolor A3(2) mutants blocked in undecylprodigiosin (Red) biosynthesis. Mol Gen Genet 227:28–32 [CrossRef]
    [Google Scholar]
  15. Cooksey R. C., Thorne G. M., Farrar W. E. Jr 1976; R factor-mediated antibiotic resistance in Serratia marcescens . Antimicrob Agents Chemother 10:123–127 [CrossRef]
    [Google Scholar]
  16. Coulthurst S. J., Kurz C. L., Salmond G. P. C. 2004; luxS mutants of Serratia defective in autoinducer-2-dependant ‘quorum sensing’ show strain-dependent impacts on virulence, carbapenem and prodigiosin production. Microbiology 150:1901–1910 [CrossRef]
    [Google Scholar]
  17. Crow M. A. 2001 The genetic regulation of pigment and antibiotic biosynthesis in Serratia sp. PhD thesis: University of Cambridge;
    [Google Scholar]
  18. D'Alessio R., Bargiotti A., Carlini O. 10 other authors 2000; Synthesis and immunosuppressive activity of novel prodigiosin derivatives. J Med Chem 43:2557–2565 [CrossRef]
    [Google Scholar]
  19. Dauenhauer S. A., Hull R. A., Williams R. P. 1984; Cloning and expression in Escherichia coli of Serratia marcescens genes encoding prodigiosin biosynthesis. J Bacteriol 158:1128–1132
    [Google Scholar]
  20. Delcher A. L., Harmon D., Kasif S., White O., Salzberg S. L. 1999; Improved microbial gene identification with GLIMMER. Nucleic Acids Res 27:4636–4641 [CrossRef]
    [Google Scholar]
  21. Demain A. L. 1995; Why do microorganisms produce antimicrobials?. In Fifty Years of Antimicrobials: Past Perspectives and Future Trends (Society for General Microbiology Symposium no 53 pp 205–228 Edited by Hunter P. A., Darby G. K., Russell N. J. Cambridge: Cambridge University Press;
    [Google Scholar]
  22. Ding M. J., Williams R. P. 1983; Biosynthesis of prodigiosin by white strains of Serratia marcescens isolated from patients. J Clin Microbiol 17:476–480
    [Google Scholar]
  23. Feitelson J. S., Malpartida F., Hopwood D. A. 1985; Genetic and biochemical characterization of the red gene cluster of Streptomyces coelicolor A3(2). J Gen Microbiol 131:2431–2441
    [Google Scholar]
  24. Flyg C., Kenne K., Boman H. G. 1980; Insect pathogenic properties of Serratia marcescens: phage-resistant mutants with a decreased resistance to Cecropia immunity and a decreased virulence toDrosophila . J Gen Microbiol 120:173–181
    [Google Scholar]
  25. Grimont P. A. D., Grimont F. 1978; The genus Serratia. Annu Rev Microbiol 32:221–248 [CrossRef]
    [Google Scholar]
  26. Grimont P. A. D., Grimont F. 1984; Genus VIII Serratia. In Bergey's Manual of Systematic Bacteriology vol 1 pp 477–484 Edited by Kreig N. R., Holt J. G. Baltimore: Williams & Wilkins;
    [Google Scholar]
  27. Harris A. K. P. 2003 Analysis of quorum sensing and prodigiosin biosynthetic genes in Serratia marcescens PhD thesis: University of Cambridge;
    [Google Scholar]
  28. Herzberg O., Chen C. C., Kapadia G., McGuire M., Carroll L. J., Noh S. J., Dunaway-Mariano D. 1996; Swiveling-domain mechanism for enzymatic phosphotransfer between remote reaction sites. Proc Natl Acad Sci U S A 93:2652–2657 [CrossRef]
    [Google Scholar]
  29. Hines D. A., Saurugger P. N., Ihler G. M., Benedik M. J. 1988; Genetic analysis of extracellular proteins of Serratia marcescens.. J Bacteriol 170:4141–4146
    [Google Scholar]
  30. Holland S., Dale J. W. 1978; The effect of resistance plasmids on pigmentation of Serratia marcescens. Microbios Lett 9:85–89
    [Google Scholar]
  31. Horng Y. T., Deng S. C., Daykin M. 7 other authors 2002; The LuxR family protein SpnR functions as a negative regulator of N-acylhomoserine lactone-dependent quorum sensing in Serratia marcescens. Mol Microbiol 45:1655–1671 [CrossRef]
    [Google Scholar]
  32. Lambalot R. H., Gehring A. M., Flugel R. S., Zuber P., LaCelle M., Marahiel M. A., Reid R., Khosla C., Walsh C. T. 1996; A new enzyme superfamily – the phosphopantetheinyl transferases. Chem Biol 3:923–936 [CrossRef]
    [Google Scholar]
  33. Lewis T. A., Cortese M. S., Sebat J. L., Green T. L., Lee C. H., Crawford R. L. 2000; A Pseudomonas stutzeri gene cluster encoding the biosynthesis of the CCl4-dechlorination agent pyridine-2,6-bis(thiocarboxylic acid. Environ Microbiol 2:407–416 [CrossRef]
    [Google Scholar]
  34. Matsuyama T., Bhasin A., Harshey R. M. 1995; Mutational analysis of flagellum-independent surface spreading of Serratia marcescens 274 on a low-agar medium. J Bacteriol 177:987–991
    [Google Scholar]
  35. McGowan S., Sebaihia M., Jones S. 7 other authors 1995; Carbapenem antibiotic production in Erwinia carotovora is regulated By CarR, a homolog of the Lux transcriptional activator. Microbiology 141:541–550 [CrossRef]
    [Google Scholar]
  36. Melvin M. S., Wooton K. E., Rich C. C., Saluta G. R., Kucera G. L., Lindquist N., Manderville R. A. 2001; Copper-nuclease efficiency correlates with cytotoxicity for the 4-methoxypyrrolic natural products. J Inorg Biochem 87:129–135 [CrossRef]
    [Google Scholar]
  37. Montaner B., Navarro S., Vilaseca M., Martinell M., Giralt E., Gil J, Piqué M., Peréz-Tomás R. 2000; Prodigiosin from the supernatant of Serratia marcescens induces apoptosis in haematopoietic cancer cell lines. Br J Pharmacol 131:585–593 [CrossRef]
    [Google Scholar]
  38. Morrison D. A. 1966; Prodigiosin synthesis in mutants of Serratia marcesens. J Bacteriol 91:1599–1604
    [Google Scholar]
  39. Mortellaro A., Songia S., Gnocchi P., Ferrari M., Fornasiero C., D'Alessio R., Isetta A., Colotta F., Golay J. 1999; New immunosuppressive drug PNU156804 blocks IL-2-dependent proliferation and NF-kappa B and AP-1 activation. J Immunol 162:7102–7109
    [Google Scholar]
  40. Park G., Tomlinson J. T., Melvin M. S., Wright M. W., Day C. S., Manderville R. A. 2003; Zinc and copper complexes of prodigiosin: implications for copper-mediated double-strand DNA cleavage. Org Lett 5:113–116 [CrossRef]
    [Google Scholar]
  41. Petersen C., Møller L. B. 2000; Control of copper homeostasis in Escherichia coli by a P-type ATPase, CopA, and a MerR-like transcriptional activator, CopR. Gene 261:289–298 [CrossRef]
    [Google Scholar]
  42. Rensing C., Fan B., Sharma R., Mitra B., Rosen B. P. 2000; CopA: an Escherichia coli Cu(I)-translocating P-type ATPase. Proc Natl Acad Sci U S A 97:652–656 [CrossRef]
    [Google Scholar]
  43. Reuter K., Mofid M. R., Marahiel M. A., Ficner R. 1999; Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4′-phosphopantetheinyl transferase superfamily. EMBO J 18:6823–6831 [CrossRef]
    [Google Scholar]
  44. Rudd B. A., Hopwood D. A. 1980; A pigmented mycelial antibiotic in Streptomyces coelicolor: Control by a chromosomal gene cluster. J Gen Microbiol 119:333–340
    [Google Scholar]
  45. Rutherford K., Parkhill J., Crook J., Horsnell T., Rice P., Rajandream M. A., Barrell B. 2000; Artemis: sequence visualization and annotation. Bioinformatics 16:944–945 [CrossRef]
    [Google Scholar]
  46. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  47. Slater H., Crow M., Everson L., Salmond G. P. 2003; Phosphate availability regulates biosynthesis of two antibiotics, prodigiosin and carbapenem, in Serratia via both quorum-sensing-dependent and -independent pathways. Mol Microbiol 47:303–320
    [Google Scholar]
  48. Staden R. 1996; The Staden sequence analysis package. Mol Biotechnol 5:233–241 [CrossRef]
    [Google Scholar]
  49. Stock I., Grueger T., Wiedemann B. 2003; Natural antibiotic susceptibility of strains of Serratia marcescens and the S. liquefaciens complex: S. liquefaciens sensu stricto, S. proteamaculans and S. grimesii . Int J Antimicrob Agents 22:35–47
    [Google Scholar]
  50. Stoyanov J. V., Hobman J. L., Brown N. L. 2001; CueR (YbbI) of Escherichia coli is a MerR family regulator controlling expression of the copper exporter CopA. Mol Microbiol 39:502–511 [CrossRef]
    [Google Scholar]
  51. Summers A. O. 1992; Untwist and shout: a heavy metal-responsive transcriptional regulator. J Bacteriol 174:3097–3101
    [Google Scholar]
  52. Summers R. G., Wendt-Pienkowski E., Motamedi H., Hutchinson C. R. 1992; Nucleotide sequence of the tcmII-tcmIV region of the tetracenomycin C biosynthetic gene cluster of Streptomyces glaucescens and evidence that the tcmN gene encodes a multifunctional cyclase-dehydratase-O-methyl transferase. J Bacteriol 174:1810–1820
    [Google Scholar]
  53. Thomas M. G., Burkart M. D., Walsh C. T. 2002; Conversion of l-proline to pyrrolyl-2-carboxyl-S-PCP during undecylprodigiosin and pyoluteorin biosynthesis. Chem Biol 9:171–184 [CrossRef]
    [Google Scholar]
  54. Thomson N. R., Cox A., Bycroft B. W., Stewart G. S., Williams P., Salmond G. P. 1997; The rap and hor proteins of Erwinia, Serratia and Yersinia: a novel subgroup in a growing superfamily of proteins regulating diverse physiological processes in bacterial pathogens. Mol Microbiol 26:531–544 [CrossRef]
    [Google Scholar]
  55. Thomson N. R., Crow M. A., McGowan S. J., Cox A., Salmond G. P. 2000; Biosynthesis of carbapenem antibiotic and prodigiosin pigment in Serratia is under quorum sensing control. Mol Microbiol 36:539–556
    [Google Scholar]
  56. Tiffany K. A., Roberts D. L., Wang M., Paschke R., Mohsen A. W., Vockley J., Kim J. J. 1997; Structure of human isovaleryl-CoA dehydrogenase at 2·6 A resolution: structural basis for substrate specificity. Biochemistry 36:8455–8464 [CrossRef]
    [Google Scholar]
  57. Traub W. H. 2000; Antibiotic susceptibility of Serratia marcescens and Serratia liquefaciens . Chemotherapy 46:315–321 [CrossRef]
    [Google Scholar]
  58. Tsao S. W., Rudd B. A., He X. G., Chang C. J., Floss H. G. 1985; Identification of a red pigment from Streptomyces coelicolor A3(2) as a mixture of prodigiosin derivatives. J Antibiot (Tokyo) 38:128–131 [CrossRef]
    [Google Scholar]
  59. Tsuji R. F., Yamamoto M., Nakamura A., Kataoka T., Magae J., Nagai K., Yamasaki M. 1990; Selective immunosuppression of prodigiosin 25-C and FK506 in the murine immune system. J Antibiot (Tokyo) 43:1293–1301 [CrossRef]
    [Google Scholar]
  60. Tsuji R. F., Magae J., Yamashita M., Nagai K., Yamasaki M. 1992; Immunomodulating properties of prodigiosin 25-C, an antibiotic which preferentially suppresses induction of cytotoxic T cells. J Antibiot (Tokyo) 45:1295–1302 [CrossRef]
    [Google Scholar]
  61. VanBogelen R. A., Olson E. R., Wanner B. L., Neidhart F. C. 1996; Global analysis of proteins synthesised during phosphorous restriction in Escherichia coli . J Bacteriol 178:4344–4366
    [Google Scholar]
  62. Webster S. P., Alexeev D., Campopiano D. J., Watt R. M., Alexeeva M., Sawyer L., Baxter R. L. 2000; Mechanism of 8-amino-7-oxononanoate synthase: spectroscopic, kinetic, and crystallographic studies. Biochemistry 39:516–528 [CrossRef]
    [Google Scholar]
  63. White J., Bibb M. 1997; bldA dependence of undecylprodigiosin production in Streptomyces coelicolor A3(2) involves a pathway-specific regulatory cascade. J Bacteriol 179:627–633
    [Google Scholar]
  64. Williams R. P. 1973; Biosynthesis of prodigiosin, a secondary metabolite of Serratia marcescens. Appl Microbiol 25:396–402
    [Google Scholar]
  65. Williams R. P., Quadri S. M. 1980; The pigments of Serratia. In The Genus Serratia pp 31–75 Edited by Graevenitz A. Von, Rubin S. J. Boca Raton, FL: CRC Press Inc;
    [Google Scholar]
  66. Williams R. P., Gott C. L., Qadri S. M., Scott R. H. 1971; Influence of temperature of incubation and type of growth medium on pigmentation in Serratia marcescens . J Bacteriol 106:438–443
    [Google Scholar]
  67. Xu H., Wang Z. X., Schmidt J., Heide L., Li S. M. 2002; Genetic analysis of the biosynthesis of the pyrrole and carbamoyl moieties of coumermycin A1 and novobiocin. Mol Genet Genomics 268:387–396 [CrossRef]
    [Google Scholar]
  68. Yanagida N., Uozumi T., Beppu T. 1986; Specific excretion of Serratia protease through the outer membrane ofEscherichia coli . J Bacteriol 166:937–944
    [Google Scholar]
  69. Yang Y. J., Wu P. J., Livermore D. M. 1990; Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates. Antimicrob Agents Chemother 34:755–758 [CrossRef]
    [Google Scholar]
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