1887

Abstract

Regions of the ISP5230 chromosome flanking , an amino-deoxychorismate synthase gene needed for chloramphenicol (Cm) production, were examined for involvement in biosynthesis of the antibiotic. Three of four ORFs in the sequence downstream of resembled genes involved in the shikimate pathway. BLASTX searches of GenBank showed that the deduced amino acid sequences of ORF3 and ORF4 were similar to proteins encoded by monofunctional genes for chorismate mutase and prephenate dehydrogenase, respectively, while the sequence of the ORF5 product resembled deoxy--heptulosonate-7-phosphate (DAHP) synthase, the enzyme that initiates the shikimate pathway. A relationship to Cm biosynthesis was indicated by sequence similarities between the ORF6 product and membrane proteins associated with Cm export. BLASTX searches of GenBank for matches with the translated sequence of ORF1 in chromosomal DNA immediately upstream of did not detect products relevant to Cm biosynthesis. However, the presence of Cm biosynthesis genes in a 75 kb segment of the chromosome beyond ORF1 was inferred when conjugal transfer of the DNA into a blocked mutant restored Cm production. Deletions in the 75 kb segment of the wild-type chromosome eliminated Cm production, confirming the presence of Cm biosynthesis genes in this region. Sequencing and analysis located five ORFs, one of which (ORF8) was deduced from BLAST searches of GenBank, and from characteristic motifs detected in alignments of its deduced amino acid sequence, to be a monomodular nonribosomal peptide synthetase. GenBank searches did not identify ORF7, but matched the translated sequences of ORFs 9, 10 and 11 with short-chain ketoreductases, the ATP-binding cassettes of ABC transporters, and coenzyme A ligases, respectively. As has been shown for ORF2, disrupting ORF3, ORF7, ORF8 or ORF9 blocked Cm production.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-147-10-2817
2001-10-01
2019-10-22
Loading full text...

Full text loading...

/deliver/fulltext/micro/147/10/1472817a.html?itemId=/content/journal/micro/10.1099/00221287-147-10-2817&mimeType=html&fmt=ahah

References

  1. Aidoo, D. A., Barrett, K. & Vining, L. C. ( 1990; ). Plasmid transformation of Streptomyces venezuelae: modified procedures used to introduce the genes for p-aminobenzoate synthetase. J Gen Microbiol 136, 657-662.[CrossRef]
    [Google Scholar]
  2. Altschul, S. F., Madden, T. L., Schaeffer, A. A., Zhang, J., Zhang, Z., Miller, W. & Lipman, D. J. ( 1997; ). Gapped blast and psi-blast: a new generation of protein database search programs. Nucleic Acids Res 25, 3389-3402.[CrossRef]
    [Google Scholar]
  3. August, P. R., Tang, L., Yoon, Y. J. & 9 other authors ( 1998; ). Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699. Chem Biol 5, 69–79.[CrossRef]
    [Google Scholar]
  4. Biermann, 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 species. Gene 160, 25-31.
    [Google Scholar]
  5. Blanc, V., Gil, P., Bamas-Jacques, N. & 8 other authors ( 1997; ). Identification and analysis of genes from Streptomyces pristinaespiralis encoding enzymes involved in the biosynthesis of the 4-dimethylamino-l-phenylalanine precursor of pristinamycin I. Mol Microbiol 23, 191–202.[CrossRef]
    [Google Scholar]
  6. Brown, M. P., Aidoo, K. A. & Vining, L. C. ( 1996; ). A role for pabAB, a p-aminobenzoate synthase gene of Streptomyces venezuelae ISP5230 in chloramphenicol biosynthesis. Microbiology 142, 1345-1355.[CrossRef]
    [Google Scholar]
  7. Bult, C. J., White, O., Olsen, G. J. & 37 other authors ( 1996; ). Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science 273, 1058–1073.[CrossRef]
    [Google Scholar]
  8. Chang, Z. (1999). Genes for cysteine biosynthesis and metabolism in Streptomyces venezuelae ISP5230: cloning, sequencing, functional analysis and relevance to chloramphenicol biosynthesis. PhD thesis, Dalhousie University, Halifax, NS, Canada.
  9. Chen, H. & Walsh, C. T. ( 2001; ). Coumarin formation in novobiocin biosynthesis: β-hydroxylation of the aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 NovI. Chem Biol 74, 1-12.
    [Google Scholar]
  10. Chen, S., von Bamberg, D., Hale, V., Breuer, M., Hardt, B., Muller, R., Floss, H. G., Reynolds, K. A. & Leistner, E. ( 1999; ). Biosynthesis of ansatrienin (mycotrienin) and naphthomycin. Identification and analysis of two separate biosynthetic gene clusters in Streptomyces collinus Tu1892. Eur J Biochem 261, 98-107.[CrossRef]
    [Google Scholar]
  11. Chong, P. P., Podmore, S. M., Kieser, H. M., Redenbach, M., Turgay, K., Marahiel, M., Hopwood, D. A. & Smith, C. P. ( 1998; ). Physical identification of a chromosomal locus encoding biosynthetic genes for the lipopeptide calcium-dependent antibiotic (CDA) of Streptomyces coelicolor A3(2). Microbiology 144, 193-199.[CrossRef]
    [Google Scholar]
  12. de Crecy-Lagard, V., Blanc, V., Gil, P., Naudin, L., Laurenzon, S., Famechon, A., Bamas-Jacques, N., Crouzet, J. & Thibaut, D. ( 1997; ). Pristinamycin I biosynthesis in Streptomyces pristinaespiralis: molecular characterization of the first two structural peptide synthetase genes. J Bacteriol 179, 705-713.
    [Google Scholar]
  13. Desomer, J., Vereecke, D., Crespi, M. & Van Montagu, M. ( 1992; ). The plasmid-encoded chloramphenicol-resistance protein of Rhodococcus fascians is homologous to the transmembrane tetracycline efflux proteins. Mol Microbiol 6, 2377-2385.[CrossRef]
    [Google Scholar]
  14. Devereux, J., Haeberli, P. & Smithies, O. ( 1984; ). A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 12, 387-395.[CrossRef]
    [Google Scholar]
  15. Dittrich, W., Betzler, M. & Schrempf, H. ( 1991; ). An amplifiable and deletable chloramphenicol-resistance determinant of Streptomyces lividans 1326 encodes a putative transmembrane protein. Mol Microbiol 5, 2789-2797.[CrossRef]
    [Google Scholar]
  16. Doull, J., Ahmed, Z., Stuttard, C. & Vining, L. C. ( 1985; ). Isolation and characterization of Streptomyces venezuelae mutants blocked in chloramphenicol biosynthesis. J Gen Microbiol 131, 97-104.
    [Google Scholar]
  17. Doull, J. L., Vats, S., Chaliciopoulos, M., Stuttard, C., Wong, K. & Vining, L. C. ( 1986; ). Conjugational fertility and location of chloramphenicol biosynthesis genes on the chromosomal linkage map of Streptomyces venezuelae. J Gen Microbiol 132, 1327-1338.
    [Google Scholar]
  18. Dyer, W. E., Weaver, L. M., Zhao, J., Kuhn, D. N., Weller, S. C. & Hermann, K. M. ( 1990; ). A cDNA encoding 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase from Solanum tuberosum L. J Biol Chem 265, 1608-1614.
    [Google Scholar]
  19. Facey, S. J., Gross, F., Vining, L. C., Yang, K. & van Pee, K. H. ( 1996; ). Cloning, sequencing and disruption of a bromoperoxidase-catalase gene in Streptomyces venezuelae. Microbiology 142, 657-665.[CrossRef]
    [Google Scholar]
  20. Flett, F., Mersinias, V. & Smith, C. P. ( 1997; ). High efficiency intergeneric conjugal transfer of plasmid DNA from Escherichia coli to methyl-DNA-restricting streptomycetes. FEMS Microbiol Lett 155, 223-229.[CrossRef]
    [Google Scholar]
  21. Gil, J. A. & Hopwood, D. A. ( 1983; ). Cloning and expression of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. J Bacteriol 174, 5317-5323.
    [Google Scholar]
  22. Hanahan, D. ( 1983; ). Studies on transformation of Escherichia coli with plasmids. J Mol Biol 166, 557-580.[CrossRef]
    [Google Scholar]
  23. Hofmann, K. & Stoffel, W. ( 1993; ). Tmbase – a database of membrane spanning protein segments. Biol Chem Hoppe–Seyler 347, 166.
    [Google Scholar]
  24. Hopwood, D. A. ( 1967; ). Genetic analysis and genome structure in Streptomyces coelicolor. Bacteriol Rev 31, 373-403.
    [Google Scholar]
  25. Hopwood, D. A., Bibb, M. J., Chater, K. F. & 7 other authors (1985). Genetic Manipulation of Streptomyces: a Laboratory Manual. Norwich: John Innes Foundation.
  26. Hori, K., Yamamoto, Y., Minetoki, T., Kurotsu, T., Kanda, M., Miura, S., Okamura, K., Furuyama, J. & Saito, Y. ( 1989; ). Molecular cloning and nucleotide sequence of the gramicidin S synthetase I gene. J Biochem 106, 639-645.
    [Google Scholar]
  27. Ishikawa, J. & Hotta, K. ( 1999; ). Frameplot: a new implementation of the frame analysis for predicting protein-coding regions in bacterial DNA with a high G+C content. FEMS Microbiol Lett 174, 251-253.[CrossRef]
    [Google Scholar]
  28. Jones, A., Francis, M. M., Vining, L. C. & Westlake, D. W. S. ( 1978; ). Biosynthesis of chloramphenicol in Streptomyces sp. 3022a. Properties of an aminotransferase accepting p-aminophenylalanine as a substrate. Can J Microbiol 24, 238-244.[CrossRef]
    [Google Scholar]
  29. Keller, U. & Schlumbohm, W. ( 1992; ). Purification and characterization of actinomycin synthetase I, a 4-methyl-3-hydroxyanthranilic acid-AMP ligase from Streptomyces chrysomallus. J Biol Chem 267, 11745-11752.
    [Google Scholar]
  30. Komatsu, T., Ohta, M., Kido, N., Arakawa, Y., Ito, H., Mizuno, T. & Kato, N. ( 1990; ). Molecular characterization of an Enterobacter cloacae gene (romA) which pleiotropically inhibits the expression of Escherichia coli outer membrane proteins. J Bacteriol 172, 4082-4089.
    [Google Scholar]
  31. Konz, D. & Marahiel, M. A. ( 1999; ). How do peptide synthetases generate structural diversity? Chem Biol 6, R39-R48.[CrossRef]
    [Google Scholar]
  32. Larson, J. L. & Hershberger, C. L. ( 1986; ). The minimal replicon of a streptomycete plasmid produces an ultrahigh level of plasmid DNA. Plasmid 15, 199-209.[CrossRef]
    [Google Scholar]
  33. Levine, J. & Fischbach, H. ( 1951; ). The chemical determination of chloramphenicol in biological materials. Antibiot Chemother 1, 59-62.
    [Google Scholar]
  34. MacNeil, D. J., Gewain, K. M., Rudy, C. L., Dezeny, G., Gibbons, P. H. & MacNeil, T. ( 1992; ). Analysis of Streptomyces avermitilis genes required for avermectin biosynthesis utilizing a novel integration vector. Gene 111, 61-68.[CrossRef]
    [Google Scholar]
  35. Malik, V. S. & Vining, L. C. ( 1970; ). Metabolism of chloramphenicol by the producing organism. Can J Microbiol 16, 173-179.[CrossRef]
    [Google Scholar]
  36. Marahiel, M. A., Stachelhaus, T. & Mootz, H. D. ( 1997; ). Modular peptide synthetases involved in nonribosomal peptide synthesis. Chem Rev 97, 2651-2673.[CrossRef]
    [Google Scholar]
  37. Mavrodi, D. V., Ksenzenko, V. N., Bonsall, R. F., Cook, R. J., Boronin, A. M. & Thomashow, L. S. ( 1998; ). A seven-gene locus for synthesis of phenazine-1-carboxylic acid by Pseudomonas fluorescens 2-79. J Bacteriol 180, 2541-2548.
    [Google Scholar]
  38. Mazodier, P., Petter, R. & Thompson, C. ( 1989; ). Intergeneric conjugation between Escherichia coli and Streptomyces species. J Bacteriol 171, 3583-3585.
    [Google Scholar]
  39. Morita, N. & Okuyama, H. ( 1999; ). Cloning and sequencing of clustered genes involved in fatty acid biosynthesis from docosahexaenoic acid-producing bacterium Vibrio marinus strain MP-1. Biotechnol Lett 21, 641-646.[CrossRef]
    [Google Scholar]
  40. Morris, M. E. & Jinks-Robertson, S. ( 1991; ). Nucleotide sequence of the LYS2 gene of Saccharomyces cerevisiae: homology to Bacillus brevis tyrocidine synthetase I. Gene 98, 141-145.[CrossRef]
    [Google Scholar]
  41. Mosher, R. H., Camp, D. J., Yang, K., Brown, M. P., Shaw, W. V. & Vining, L. C. ( 1995; ). Inactivation of chloramphenicol by O-phosphorylation. J Biol Chem 270, 27000-27006.[CrossRef]
    [Google Scholar]
  42. Nagy, I., Schoofs, G., Vanderleyden, J. & De Mot, R. ( 1997; ). Transposition of the IS21-related element IS1415 in Rhodococcus erythropolis. J Bacteriol 179, 4635-4638.
    [Google Scholar]
  43. Nichols, B. P., Seibold, A. M. & Doktor, S. Z. ( 1989; ). para-Aminobenzoate biosynthesis from chorismate occurs in two steps. J Biol Chem 264, 8597-8601.
    [Google Scholar]
  44. Paradkar, A. S. & Jensen, S. E. ( 1995; ). Functional analysis of the gene encoding the clavaminate synthase 2 isoenzyme involved in clavulanic acid biosynthesis in Streptomyces clavuligerus. J Bacteriol 177, 1307-1314.
    [Google Scholar]
  45. Pittard, A. J. ( 1996; ). Biosynthesis of aromatic amino acids. In Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology , pp. 458-484. Edited by F. C. Neidhardt, R. Curtiss III, J. L. Ingraham, E. C. C. Lin, K. Brooks Law, B. Magasanik, W. S. Reznikoff, M. Riley, M. Schaechter & H. E. Umbarger. Washington, DC:American Society for Microbiology.
  46. Pospiech, A., Bietenhader, J. & Schupp, T. ( 1996; ). Two multifunctional peptide synthetases and an O-methyltransferase are involved in biosynthesis of the DNA-binding antibiotic and antitumour agent saframycin Mx1 from Myxococcus xanthus. Microbiology 142, 741-746.[CrossRef]
    [Google Scholar]
  47. Rao, R. N., Allen, N. E., Hobbs, J. N.Jr, Alborn, W. E.Jr, Kirst, H. A. & Paschal, J. W. ( 1983; ). Genetic and enzymatic basis for hygromycin B resistance in E. coli. Antimicrob Agents Chemother 24, 689-695.[CrossRef]
    [Google Scholar]
  48. Ruan, X., Stassi, D., Lax, S. A. & Katz, L. ( 1997; ). A second type-I PKS gene cluster isolated from ATCC 29253, a rapamycin-producing strain. Gene 203, 1-9.[CrossRef]
    [Google Scholar]
  49. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  50. Slock, J., Stahly, D. P., Han, C.-Y., Six, E. W. & Crawford, I. P. ( 1990; ). An apparent Bacillus subtilis folic acid biosynthetic operon containing pab, an amphibolic trpG gene, a third gene required for synthesis of para-aminobenzoic acid and the dihydropteroate synthetase gene. J Bacteriol 172, 7211-7226.
    [Google Scholar]
  51. Stuttard, C. ( 1982; ). Temperate phages of Streptomyces venezuelae: lysogeny and host specificity shown by SV1 and SV2. J Gen Microbiol 128, 115-121.
    [Google Scholar]
  52. Teng, C. Y., Ganem, B., Doktor, S., Nichols, B. P., Bhatnagar, R. K. & Vining, L. C. ( 1985; ). Total biosynthesis of 4-amino-4-deoxychorismic acid: a key intermediate in the biosynthesis of p-aminobenzoic acid and l-p-aminophenylalanine. J Am Chem Soc 107, 5008-5009.[CrossRef]
    [Google Scholar]
  53. Tinoco, I.Jr, Borer, P. N., Dengler, B., Levine, M. D., Uhlenbeck, O. C., Crothers, D. M. & Gralla, J. ( 1973; ). Improved estimation of secondary structure in ribonucleic acids. Nature New Biol 246, 40-41.[CrossRef]
    [Google Scholar]
  54. Vats, S., Stuttard, C. & Vining, L. C. ( 1987; ). Transductional analysis of chloramphenicol biosynthesis genes in Streptomyces venezuelae. J Bacteriol 169, 3809-3813.
    [Google Scholar]
  55. Vining, L. C. & Stuttard, C. ( 1994; ). Chloramphenicol. In Genetics and Biochemistry of Antibiotic Production , pp. 505-530. Edited by L. C. Vining & C. Stuttard. Boston:Butterworth–Heinemann.
  56. Vining, L. C. & Westlake, D. W. S. ( 1984; ). Chloramphenicol: properties, biosynthesis and fermentation. In Biotechnology of Industrial Antibiotics , pp. 387-411. Edited by S. J. Vandamme. New York & Basel:Marcel Dekker.
  57. Wright, F. & Bibb, M. J. ( 1992; ). Codon usage in the G+C-rich Streptomyces genome. Gene 113, 55-65.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-147-10-2817
Loading
/content/journal/micro/10.1099/00221287-147-10-2817
Loading

Data & Media loading...

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