1887

Abstract

The nucleotide sequence on both sides of the polyketide synthase gene of the erythromycin-producing bacterium reve the presence of ten genes that are involved in -mycarose () and -desosamine () biosynthesis or attachment. Mutant strains carrying targeted lesions in eight of these genes indicate that three ( an ) act in L-mycairose biosynthesis or attachment, while the other five ( and ) are devoted to -desosamine biosynthesis or attachment. The remaining two genes ( and ) appear to function in -mycarose biosynthesis based on computer analysis an earlier genetic data. Three of these genes, and , lie between the and genes on one side of the polyketide synthase genes, while the remaining seven, and lie upstream of the gene on the other side of the gene cluster. The deduced products of these genes show similarities to: aldohexos 4-ketoreductases (), aldoketo reductases (), aldohexose 5-epimerases (), the gene of the daunomycin biosynthetic pathwa of (), glycosyltransferases ( and ), the AscC 3,4-dehydratase from the ascarylose biosynthetic pathway of (), and mammalian -methyltransferases (). The gene resembles a cytochrome P450, but lacks the conserved cysteir residue responsible for coordination of the haem iron, while the gene displays no meaningful similarity to other known sequences. From the predicted function of these and other known and genes, pathways for the biosynthesis of L-mycarose and D-desosamine have been deduced.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-143-10-3251
1997-10-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/143/10/mic-143-10-3251.html?itemId=/content/journal/micro/10.1099/00221287-143-10-3251&mimeType=html&fmt=ahah

References

  1. Altschul S.F., Gish W., Miller W., Myers E.W., Lipman D.J. 1990; Basic local alignment search tool. J Mol Biol 215:403–410
    [Google Scholar]
  2. Bauer A.J., Rayment I., Frey P.A., Holden H.M. 1992; The molecular structure of udp-galactose 4-epimerase from escherichia coli determined at 2·5 a resolution. Proteins 12:372–381
    [Google Scholar]
  3. Bevitt D.J., Cortes J., Haydock S.F., Leadlay P.F. 1992; 6-deoxyerythronolide b synthase 2 from saccharopolyspora ery-thraea. Cloning of the structural gene, sequence analysis and inferred domain structure of the multifunctional enzyme. Eur J Biochem 204:39–49
    [Google Scholar]
  4. Bibb M.J., Cohen S.N. 1982; Gene expression in streptomyces: Construction and application of promoter-probe plasmid vectors in Streptomyces lividans . Mol Gen Genet 187:265–277
    [Google Scholar]
  5. Cortes J., Haydock S.F., Roberts G.A., Bevitt D.J., Leadlay P.F. 1990; An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea . Nature 348:176–178
    [Google Scholar]
  6. Denoya C., Dubnau D. 1989; Monoand dimethylating activities and kinetic studies of the ermc 23 s rrna methyl transferase. J Biol Chem 264:2615–2624
    [Google Scholar]
  7. Devereux J., Haeberli P., Smithies O. 1984; A comprehensive set of sequence analysis programs for the vax. Nucleic Acids Res 12:387–395
    [Google Scholar]
  8. Dhillon N., Hale R.S., Cortes J., Leadlay P.F. 1989; Molecular characterization of a gene from saccharopolyspora erythraea (streptomyces erythraeus) which is involved in erythromycin biosynthesis. Mol Microbiol 3:1405–1414
    [Google Scholar]
  9. Dickens M.L., Ye J., Strohl W.R. 1996; Cloning, Sequencing, and Analysis of Aklaviketone Reductase from Streptomyces Sp. Strain C5. J Bacteriol 178:3384–3388
    [Google Scholar]
  10. Donadio S., Katz L. 1992; Organization of the enzymatic domains in the multifunctional polyketide synthase involved in erythromycin formation in Saccharopolyspora erythraea . Gene 111:551–560
    [Google Scholar]
  11. Donadio S., Staver M.J. 1993; IS1136, an Insertion Element in the Erythromycin Gene Cluster of Saccharopolyspora erythraea . Gene 126:147–151
    [Google Scholar]
  12. Donadio S., Staver M.J., McAlpine J.B., Swanson S.J., Katz L. 1991; Modular organization of genes required for complex polyketide biosynthesis. Science 252:675–679
    [Google Scholar]
  13. Donadio S., Stassi D., McAlpine J.B. 9 Other Authors 1993; Recent developments in the genetics of erythromycin formation. In Industrial Microorganisms: Basic and Applied Molecular Genetics pp. 257–265 Edited by Baltz R. H., Hegeman G. D., Skatrud P. L. Washington, DC: American Society for Microbiology;
    [Google Scholar]
  14. Ellis E.M., Judah D.J., Neal G.E., Hayes J.D. 1993; An Ethoxyquin-Inducible Aldehyde Reductase from Rat Liver that Metabolizes Aflatoxin Bt Defines a Subfamily of Aldo-Keto Reductases. Proc Natl Acad Sci USA 90:10350–10354
    [Google Scholar]
  15. Geistlich M., Losick R., Turner J.R., Rao R.N. 1992; Characterization of a novel regulatory gene governing the expression of a polyketide synthase gene in Streptomyces ambofaciens . Mol Microbiol 6:2019–2029
    [Google Scholar]
  16. Haydock S.F., Dowson J.A., Dhillon N., Roberts G.A., Cortes J., Leadlay P.F. 1991; Cloning and sequence analysis of genes involved in erythromycin biosynthesis in saccharopolyspora erythraea: Sequence similarities between eryg and a family of sadenosylmethionine-dependent methyltransferases. Mol Gen Genet 230:120–128
    [Google Scholar]
  17. Hopwood D.A., Bibb M.J., Chater K.F., Kieser T., Bruton C.J., Kieser H.M., Lydiate D.J., Smith C.P., Ward J.M., Schrempf H. 1985 Genetic Manipulation of Streptomyces: a Laboratory Manual Norwich: John Innes Foundation;
    [Google Scholar]
  18. Jiang X.-M., Neal B., Santiago F., Lee S.J., Romana L.K., Reeves P.R. 1991; Structure and sequence of the rfb (O antigen) gene cluster of salmonella serovar typhimurium (strain lt2). Mol Microbiol 5:695–713
    [Google Scholar]
  19. Katz L., Donadio S. 1993; Polyketide synthesis: Prospects for hybrid antibiotics. Annu Rev Microbiol 47:875–912
    [Google Scholar]
  20. Kim K.-S., Farrand S.K. 1996; Ti plasmid-encoded genes responsible for catabolism of the crown gall opine mannopine by agrobacterium tumefaciens are homologs of the t-region genes responsible for synthesis of this opine by the plant tumour. J Bacteriol 178:3275–3284
    [Google Scholar]
  21. Krügel H., Schumann G., Hanel F., Fiedler G. 1993; Nucleotide sequence analysis of five putative streptomyces griseusgenes, one of which complements an early function in daunorubicin biosynthesis that is linked to a putative gene cluster involved in tdp-daunosamine formation. Mol Gen Genet 241:193–202
    [Google Scholar]
  22. Lemaire H.-G., Müller-Hill B. 1986; Nucleotide sequences of the gale and galt gene of E. coli . Nucleic Acids Res 7705:771114
    [Google Scholar]
  23. Linton K.J., Jarvis B.W., Hutchinson C.R. 1995; Cloning the genes encoding thymidine diphosphoglucose 4,6-dehydratase and thymidine diphospho-4-keto-6-deoxyglucose 3,5-epimerase from the erythromycin-producing saccharopolyspora erythraea . Gene 153:33–40
    [Google Scholar]
  24. Liu H., Thorson J.S. 1994; Pathways and mechanisms in the biogenesis of novel deoxysugars by bacteria. Annu Rev Microbiol 48:223–256
    [Google Scholar]
  25. Merson-Davies L.A., Cundliffe E. 1994; Analysis of five tylosin biosynthetic genes from the tyllba region of the streptomyces fradiae genome. Mol Microbiol 13:349–355
    [Google Scholar]
  26. Niemi J., Mäntsälä P. 1995; Nucleotide sequences and expression of genes from streptomyces purpurascens that cause the production of new anthracyclines in streptomyces galilaeus . J Bacteriol 177:2942–2945
    [Google Scholar]
  27. Ochsner U.A., Fiechter A., Reiser J. 1994; Isolation, characterization, and expression in escherichia coli of the pseudomonas aeruginosa rhlab genes encoding a rhamnosyltransferase involved in rhamnolipid biosurfactant synthesis. J Biol Chem 269:19787–19795
    [Google Scholar]
  28. Ogawa H., Konishi K., Takata Y., Nakashima H., Fujioka M. 1987; Rat glycine methyltransferase: Complete amino acid sequence deduced from a cdna clone and characterization of the genomic dna. Eur J Biochem 168:141–151
    [Google Scholar]
  29. Otten S.L., Liu X., Ferguson J., Hutchinson C.R. 1995; Cloning and characterization of the streptomyces peucetius dnrqs genes encoding a daunosamine biosynthesis enzyme and a glycosyl transferase involved in daunorubicin biosynthesis. J Bacteriol 177:6688–6692
    [Google Scholar]
  30. Paulus T.J., Tuan J.S., Luebke V.I., Maine G.T., DeWitt J.P., Katz L. 1990; Mutation and cloning of eryg, the structural gene for erythromycin o-methyltransferase from saccharopolyspora erythraea, and expression of eryg in Escherichia coli . J Bacteriol 172:2541–2546
    [Google Scholar]
  31. Pereda A., Summers R.G., Katz L. 1997; Nucleotide sequence of the erme distal flank of the erythromycin biosynthesis cluster in Saccharopolyspora erythraea . Gene 193:65–71
    [Google Scholar]
  32. Pissowotzki K., Mansouri K., Piepersberg W. 1991; Genetics of streptomycin production in streptomyces griseus: Molecular structure and putative function of genes strELMBZN . Mol Gen Genet 231:113–123
    [Google Scholar]
  33. Queener S.W., Sebek O.K., Vlzina C. 1978; Mutants blocked in antibiotic synthesis. Annu Rev Microbiol 32:
    [Google Scholar]
  34. Reiser J., Muheim A., Hardegger M., Frank G., Fiechter A. 1994; Aryl-Alcohol Dehydrogenase from the White-Rot Fungus Phanerochaete chrysosporium . J Biol Chem 269:28152–28159
    [Google Scholar]
  35. Rettig J., Heinemann S.H., Wunder F., Lorra C., Parcej D.N., Dolly J.D., Pongs O. 1994; Inactivation properties of voltagegated k+ channels altered by presence of β-subunit. Nature 369:289–294
    [Google Scholar]
  36. 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]
  37. Schulman M.D., Acton S.L., Valentino D.L., Arison B.H. 1990; Purification and Identification of Dtdp-Oleandrose, the Precursor of the Oleandrose Units of the Avermectins. J Biol Chem 265:16965–16970
    [Google Scholar]
  38. Scotti C., Hutchinson C.R. 1996; Enhanced antibiotic production by manipulation of the streptomyces peucetius dnrh and dnmt genes involved in doxorubicin (Adriamycin) biosynthesis. J Bacteriol 178:7316–7321
    [Google Scholar]
  39. Stanzak R., Matsushima P., Baltz R.H., Rao R.N. 1986; Cloning and expression in streptomyces lividans of clustered erythromycin biosynthesis genes from Streptomyces erythraeus . Bio/Technology 4:229–232
    [Google Scholar]
  40. Stassi D., Donadio S., Staver M.J., Katz L. 1993; Identification of a saccharopolyspora erythraea gene required for the final hydroxylation step in erythromycin biosynthesis. J Bacteriol 175:182–189
    [Google Scholar]
  41. Stutzman-Engwall K.J., Often S.L., Hutchinson G.R. 1992; Regulation of secondary metabolism in streptomyces spp. And overproduction of daunorubicin in streptomyces peucetius . J Bacteriol 174:144–154
    [Google Scholar]
  42. Thorson J.S., Lo S.F., Liu H., Hutchinson C.R. 1993; Biosynthesis of 3,6-dideoxyhexoses: New mechanistic reflections upon 2,6-dideoxy, 4,6-dideoxy, and amino sugar construction. J Am Cbem Soc 115:6993–6994
    [Google Scholar]
  43. Thorson J.S., Lo S.F., Ploux O., He X., Liu H. 1994; Studies of the biosynthesis of 3,6-dideoxyhexoses: Molecular cloning and characterization of the asc (ascarylose) region from yersinia pseudotuberculosis serogroup va. J Bacteriol 176:5483–5493
    [Google Scholar]
  44. Tuan J.S., Weber J.M., Staver M.J., Leung J.O., Donadio S., Katz L. 1990; Cloning of genes involved in erythromycin biosynthesis from saccharopolyspora erythraea using a novel actinomycete-escherichia coli cosmid. Gene 90:21–29
    [Google Scholar]
  45. Uchiyama H., Weisblum B. 1985; N-methyl transferase of streptomyces erythraeus that confers resistance to the macrolide- lincosamide-streptogramin b antibiotics: Amino acid sequence and its homology to cognate r-factor enzymes from pathogenic bacilli and cocci. Gene 38:103–110
    [Google Scholar]
  46. Vara J.A., Hutchinson C.R. 1988; Purification of thymidine- diphospho-d-glucose 4,6-dehydratase from an erythromycin producing strain of saccharopolyspora erythraea by high resolution liquid chromatography. J Biol Cbem 263:14992–14995
    [Google Scholar]
  47. Vara J., Lewandowska-Skarbek M., Wang Y.-G., Donadio S., Hutchinson C.R. 1989; Cloning of genes governing the deoxysugar portion of the erythromycin biosynthesis pathway in saccharopolyspora erythraea (streptomyces erythraeus). J Bacteriol 171:5872–5881
    [Google Scholar]
  48. Weber J.M., Losick R. 1988; The use of a chromosome integration vector to map erythromycin resistance and production genes in saccharopolyspora erythraea(streptomyces erythraeus). Gene 68:173–180
    [Google Scholar]
  49. Weber J.M., Wierman C.K., Hutchinson C.R. 1985; Genetic Analysis of Erythromycin Production in Streptomyces erythraeus . J Bacteriol 164:425–433
    [Google Scholar]
  50. Weber J.M., Schoner B., Losick R. 1989; Identification of a gene required for the terminal step in erythromycin a biosynthesis in saccharopolyspora erythraea (streptomyces erythraeus). Gene 75:235–241
    [Google Scholar]
  51. Weber J.M., Leung J.O., Maine G.T., Potenz R.H.B., Paulus T.J., Dewitt J.P. 1990; Organization of a cluster of erythromycin genes in Saccharopolyspora erythraea . J Bacteriol 172:2372–2383
    [Google Scholar]
  52. Weber J.M., Leung J.O., Swanson S.J., Idler K.B., McAlpine J.B. 1991; An erythromycin derivative produced by targeted gene disruption in saccharopolyspora erythraea . Science 252:114–117
    [Google Scholar]
  53. Weigel T.M., Liu L., Liu H. 1992; Mechanistic studies of the biosynthesis of 3,6-dideoxyhexoses in yersinia pseudotuberculosis: Purification and characterization of cdp-4-keto-6-deoxyd-glucose-3-dehydrase. Biochemistry 31:2129–2139
    [Google Scholar]
  54. Wierenga R.K., Hoi W.G.J. 1983; Predicted nucleotidebinding properties of p21 protein and its cancer-associated variant. Nature 302:842–844
    [Google Scholar]
  55. Wyk P., Reeves P. 1989; Identification and sequence of the gene for abequose synthase, which confers antigenic specificity on group b salmonellae: Homology with galactose epimerase. J Bacteriol 171:5687–5693
    [Google Scholar]
  56. Xiang S.-H., Hobbs M., Reeves P.R. 1994; Molecular analysis of the rfb gene cluster of a group d2 salmonella enterica strain: Evidence for its origin from an insertion sequence-mediated recombination event between group e and d1 strains. J Bacteriol 176:4357–4365
    [Google Scholar]
  57. Yamamoto H., Maurer K.H., Hutchinson C.R. 1986; Transformation of streptomyces erythraeus . J Antibiotics 39:
    [Google Scholar]
  58. Yamamoto-Otake H., Nakano E., Koyama Y. 1994; Cloning and sequencing of the l-fucose dehydrogenase gene from pseudomonas sp. No.1143. Biosci Biotech Biochem 58:2281–2282
    [Google Scholar]
  59. Yanisch-Perron C., Vieira J., Messing J. 1985; Improved m13 phage cloning vectors and host strains: Nucleotide sequences of the m13mpl8 and puc19 vectors. Gene 33:103–119
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-143-10-3251
Loading
/content/journal/micro/10.1099/00221287-143-10-3251
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