Skip to main content
SpringerLink
Log in

Avoidance of suicide in antibiotic-producing microbes

  • Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Many microbes synthesize potentially autotoxic antibiotics, mainly as secondary metabolites, against which they need to protect themselves. This is done in various ways, ranging from target-based strategies (i.e. modification of normal drug receptors or de novo synthesis of the latter in drug-resistant form) to the adoption of metabolic shielding and/or efflux strategies that prevent drug–target interactions. These self-defence mechanisms have been studied most intensively in antibiotic-producing prokaryotes, of which the most prolific are the actinomycetes. Only a few documented examples pertain to lower eukaryotes while higher organisms have hardly been addressed in this context. Thus, many plant alkaloids, variously described as herbivore repellents or nitrogen excretion devices, are truly antibiotics—even if toxic to humans. As just one example, bulbs of Narcissus spp. (including the King Alfred daffodil) accumulate narciclasine that binds to the larger subunit of the eukaryotic ribosome and inhibits peptide bond formation. However, ribosomes in the Amaryllidaceae have not been tested for possible resistance to narciclasine and other alkaloids. Clearly, the prevalence of suicide avoidance is likely to extend well beyond the remit of the present article.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aguilera S, López-López K, Nieto Y, Garcidueñas-Piña R, Hernández-Guzmán G, Hernández-Flores JL, Murillo J, Alvarez-Morales A (2007) Functional characterization of the gene cluster from Pseudomonas syringae pv. phaseolicola NPS3121 involved in synthesis of phaseolotoxin. J Bacteriol 189:2834–2843

    CAS  PubMed  Google Scholar 

  2. Ahlert J, Shepard E, Lomovskaya N, Zazopoulos E, Staffa A, Bachmann BO, Huang K, Fonstein L, Czisny A, Whitwam RE, Farnet CM, Thorson JS (2002) The calicheamicin gene cluster and its iterative type I enediyne PKS. Science 297:1173–1176

    CAS  PubMed  Google Scholar 

  3. Anzai H, Yoneyama K, Yamaguchi I (1989) Transgenic tobacco resistant to a bacterial disease by the detoxification of a pathogenic toxin. Mol Gen Genet 219:492–494

    CAS  Google Scholar 

  4. Aparicio JF, Fouces R, Mendes MV, Olivera N, Martin JF (2000) A complex multienzyme system encoded by five polyketide synthase genes is involved in the biosynthesis of the 26-membered polyene macrolide pimaricin in Streptomyces natalensis. Chem Biol 7:895–905

    CAS  PubMed  Google Scholar 

  5. Arthur M, Courvalin P (1993) Genetics and mechanisms of glycopeptide resistance in enterococci. Antimicrob Agents Chemother 37:1563–1571

    CAS  PubMed  Google Scholar 

  6. August PR, Flickinger MC, Sherman DH (1994) Cloning and analysis of a locus (mcr) involved in mitomycin C resistance in Streptomyces lavendulae. J Bacteriol 176:4448–4454

    CAS  PubMed  Google Scholar 

  7. Ballesta JPG, Cundliffe E (1991) Site-specific methylation of 16S rRNA caused by pct, a pactamycin resistance determinant from the producing-organism, Streptomyces pactum. J Bacteriol 173:7213–7218

    CAS  PubMed  Google Scholar 

  8. Beauclerk AAD, Cundliffe E (1987) Sites of action of two ribosomal RNA methylases responsible for resistance to aminoglycosides. J Mol Biol 193:661–671

    CAS  PubMed  Google Scholar 

  9. Benveniste R, Davies J (1973) Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proc Natl Acad Sci USA 70:2276–2280

    CAS  PubMed  Google Scholar 

  10. Beyer S, Distler J, Piepersberg W (1996) The str gene cluster for the biosynthesis of 5’-hydroxystreptomycin in Streptomyces glaucescens GLAO (ETH 22794): new operons and evidence for pathway-specific regulation by StrR. Mol Gen Genet 250:775–784

    CAS  PubMed  Google Scholar 

  11. Bibb MJ, Janssen GR, Ward JM (1986) Cloning and analysis of the promoter region of the erythromycin-resistance gene (ermE) of Streptomyces erythraeus. Gene 41:E357–E368

    CAS  Google Scholar 

  12. Biggins JB, Onwueme KC, Thorson JS (2003) Resistance to enediyne antitumor antibiotics by CalC self-sacrifice. Science 301:1537–1541

    CAS  PubMed  Google Scholar 

  13. Birmingham VA, Cox KL, Larson JL, Fishman SE, Hershberger CL, Seno ET (1986) Cloning and expression of a tylosin resistance gene from a tylosin-producing strain of Streptomyces fradiae. Mol Gen Genet 204:532–539

    CAS  PubMed  Google Scholar 

  14. Blanc V, Salah-Bey K, Folcher M, Thompson CJ (1995) Molecular characterization and transcriptional analysis of a multidrug resistance gene cloned from the pristinamycin-producing organism, Streptomyces pristinaespiralis. Mol Microbiol 17:989–999

    CAS  PubMed  Google Scholar 

  15. Brautaset T, Sekurova ON, Sletta H, Ellingsen TE, Strøm AR, Valla S, Zotchev SB (2000) Biosynthesis of the polyene antifungal antibiotic nystatin in Streptomyces noursei ATCC 11455: analysis of the gene cluster and deduction of the biosynthetic pathway. Chem Biol 7:395–403

    CAS  PubMed  Google Scholar 

  16. Breukink E, Wiedemann I, van Kraaij C, Kuipers OP, Sahl H-G, de Kruijff B (1999) Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science 286:2361–2364

    CAS  PubMed  Google Scholar 

  17. Burdett V (1986) Streptococcal tetracycline resistance mediated at the level of protein synthesis. J Bacteriol 165:564–569

    CAS  PubMed  Google Scholar 

  18. Burdett V (1996) Tet(M)-promoted release of tetracycline from ribosomes is GTP dependent. J Bacteriol 178:3246–3251

    CAS  PubMed  Google Scholar 

  19. Caballero JL, Martinez E, Malpartida F, Hopwood DA (1991) Organisation and functions of the actVA region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor. Mol Gen Genet 230:401–412

    CAS  PubMed  Google Scholar 

  20. Caffrey P, Lynch S, Flood E, Finnan S, Oliynyk M (2001) Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes. Chem Biol 8:713–723

    CAS  PubMed  Google Scholar 

  21. Calcutt MJ, Cundliffe E (1990) Resistance to pactamycin in clones of Streptomyces lividans containing DNA from pactamycin-producing Streptomyces pactum. Gene 93:85–89

    CAS  PubMed  Google Scholar 

  22. Calcutt MJ, Cundliffe E (1990) Cloning of a lincosamide resistance determinant from Streptomyces caelestis, the producer of celesticetin, and characterization of the resistance mechanism. J Bacteriol 172:4710–4714

    CAS  PubMed  Google Scholar 

  23. Calcutt MJ, Schmidt FJ (1994) Gene organization in the bleomycin-resistance region of the producer organism Streptomyces verticillus. Gene 151:17–21

    CAS  PubMed  Google Scholar 

  24. Campelo AB, Gil JA (2002) The candicidin gene cluster from Streptomyces griseus IMRU 3570. Microbiology 148:51–59

    CAS  PubMed  Google Scholar 

  25. Cappellano C, Monti F, Sosio M, Donadio S, Sarubbi E (1997) Natural kirromycin resistance of elongation factor Tu from the kirrothricin producer Streptomyces cinnamoneus. Microbiology 143:617–624

    CAS  PubMed  Google Scholar 

  26. Choi S-K, Park S-Y, Kim R, Kim S-B, Lee C-H, Kim JF, Park S-H (2009) Identification of a polymyxin synthetase gene cluster of Paenibacillus polymyxa and heterologous expression of the gene in Bacillus subtilis. J Bacteriol 191:3350–3358

    CAS  PubMed  Google Scholar 

  27. Connell SR, Tracz DM, Nierhaus KH, Taylor DE (2003) Ribosomal protection proteins and their mechanism of tetracycline resistance. Antimicrob Agents Chemother 47:3675–3681

    CAS  PubMed  Google Scholar 

  28. Crameri R, Davies JE (1986) Increased production of aminoglycosides associated with amplified antibiotic resistance genes. J Antibiot 39:128–135

    CAS  PubMed  Google Scholar 

  29. Cundliffe E (1978) Mechanism of resistance to thiostrepton in the producing-organism Streptomyces azureus. Nature 272:792–795

    CAS  PubMed  Google Scholar 

  30. Cundliffe E (1989) How antibiotic-producing organisms avoid suicide. Annu Rev Microbiol 43:207–233

    CAS  PubMed  Google Scholar 

  31. Cundliffe E (1992) Resistance to macrolides and lincosamides in Streptomyces lividans and to aminoglycosides in Micromonospora purpurea. Gene 115:75–84

    CAS  PubMed  Google Scholar 

  32. Cundliffe E, Thompson J (1981) The mode of action of nosiheptide (multhiomycin) and the mechanism of resistance in the producing organism. J Gen Microbiol 126:185–192

    CAS  PubMed  Google Scholar 

  33. Davies J (1980) Enzymes modifying aminocyclitol antibiotics and their roles in resistance determination and biosynthesis. In: Rinehart KL Jr, Suami T (eds) Aminocyclitol antibiotics. Amer Chem Soc, Washington DC, pp 323–334

    Google Scholar 

  34. Davies J, Houk C, Yagisawa M, White TJ (1979) Occurrence and function of aminoglycoside-modifying enzymes. In: Sebek OK, Laskin AJ (eds) Genetics of industrial microorganisms. Amer Soc Microbiol, Washington DC, pp 166–169

    Google Scholar 

  35. D’Costa VM, McGrann KM, Hughes DW, Wright GD (2006) Sampling the antibiotic resistome. Science 311:374–377

    PubMed  Google Scholar 

  36. De Block M, Botterman J, Vandewiele M, Dockx J, Thoen C, Gosselé V, Rao Movva N, Thompson C, van Montagu M, Leemans J (1987) Engineering herbicide resistance in plants by expression of a detoxifying enzyme. EMBO J 6:2513–2518

    PubMed  CAS  Google Scholar 

  37. Demain AL (1974) How do antibiotic-producing microorganisms avoid suicide? Ann NY Acad Sci 235:601–612

    CAS  PubMed  Google Scholar 

  38. Distler J, Braun C, Ebert A, Piepersberg W (1987) Gene cluster for streptomycin biosynthesis in Streptomyces griseus: Analysis of a central region including the major resistance gene. Mol Gen Genet 208:204–210

    CAS  PubMed  Google Scholar 

  39. Dixon PD, Beven JE, Cundliffe E (1975) Properties of the ribosomes of antibiotic producers: effects of thiostrepton and micrococcin on the organisms which produce them. Antimicrob Agents Chemother 7:850–855

    CAS  PubMed  Google Scholar 

  40. Doran JL, Leskiw BK, Aippersbach S, Jensen SE (1990) Isolation and characterization of a β-lactamase-inhibitory protein from Streptomyces clavuligerus and cloning and analysis of the corresponding gene. J Bacteriol 172:4909–4918

    CAS  PubMed  Google Scholar 

  41. Dowding J, Davies J (1975) Mechanisms and origins of plasmid-determined antibiotic resistance. In: Schlessinger D (ed) Microbiology-1974. Amer Soc Microbiol, Washington DC, pp 179–186

    Google Scholar 

  42. Doyle D, McDowall KJ, Butler MJ, Hunter IS (1991) Characterization of an oxytetracycline-resistance gene, otrA, of Streptomyces rimosus. Mol Microbiol 5:2923–2933

    CAS  PubMed  Google Scholar 

  43. Feinstein E, Canaani E, Weiner LM (1993) Dependence of nucleic acid degradation on in situ free-radical production by adriamycin. Biochemistry 32:13156–13161

    CAS  PubMed  Google Scholar 

  44. Feistner GJ, Uchytil TF, Knoche KK, Durbin RD (1991) A tabtoxinine-related metabolite from Pseudomonas syringae pv. tabaci. J Org Chem 56:2922–2925

    CAS  Google Scholar 

  45. Felnagle EA, Rondon MR, Berti AD, Crosby HA, Thomas MG (2007) Identification of the biosynthetic gene cluster and an additional gene for resistance to the antituberculosis drug capreomycin. Appl Environ Microbiol 73:4162–4170

    CAS  PubMed  Google Scholar 

  46. Ferguson AR, Johnston JS, Mitchell RE (1980) Resistance of Pseudomonas syringae pv. phaseolicola to its own toxin, phaseolotoxin. FEMS Microbiol Lett 7:123–125

    CAS  Google Scholar 

  47. Fernández E, Lombó F, Méndez C, Salas JA (1996) An ABC transporter is essential for resistance to the antitumor agent mithramycin in the producer Streptomyces argillaceus. Mol Gen Genet 251:692–698

    PubMed  Google Scholar 

  48. Fernández-Moreno MA, Caballero JL, Hopwood DA, Malpartida F (1991) The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of Streptomyces. Cell 66:769–780

    PubMed  Google Scholar 

  49. Fierro JF, Hardisson C, Salas JA (1987) Resistance to oleandomycin in Streptomyces antibioticus, the producer organism. J Gen Microbiol 133:1931–1939

    CAS  PubMed  Google Scholar 

  50. Fierro JF, Hardisson C, Salas JA (1988) Involvement of cell impermeability in resistance to macrolides in some producer streptomycetes. J Antibiot 41:142–144

    CAS  PubMed  Google Scholar 

  51. Fish SA, Cundliffe E (1997) Stimulation of polyketide metabolism in Streptomyces fradiae by tylosin and its glycosylated precursors. Microbiology 143:3871–3876

    CAS  PubMed  Google Scholar 

  52. Flatman RH, Howells AJ, Heide L, Fiedler H-P, Maxwell A (2005) Simocyclinone D8, an inhibitor of DNA gyrase with a novel mode of action. Antimicrob Agents Chemother 49:1093–1100

    CAS  PubMed  Google Scholar 

  53. Floss HG, Yu T-W (2005) Rifamycin—mode of action, resistance, and biosynthesis. Chem Rev 105:621–632

    CAS  PubMed  Google Scholar 

  54. Fröhlich K-U, Kannwischer R, Rüdiger M, Mecke D (1996) Pentalenolactone-insensitive glyceraldehyde-3-phosphate dehydrogenase from Streptomyces arenae is closely related to GAPDH from thermostable eubacteria and plant chloroplasts. Arch Microbiol 165:179–186

    PubMed  Google Scholar 

  55. Fröhlich K-U, Wiedmann M, Lottspeich F, Mecke D (1989) Substitution of a pentalenolactone-sensitive glyceraldehyde-3-phosphate dehydrogenase by a genetically distinct resistant isoform accompanies pentalenolactone production in Streptomyces arenae. J Bacteriol 171:6696–6702

    PubMed  Google Scholar 

  56. Fujisawa Y, Weisblum B (1981) A family of r-determinants in Streptomyces spp. that specifies inducible resistance to macrolide, lincosamide and streptogramin type B antibiotics. J Bacteriol 146:621–631

    CAS  PubMed  Google Scholar 

  57. Furuya K, Hutchinson CR (1998) The DrrC protein of Streptomyces peucetius, a UvrA-like protein, is a DNA-binding protein whose gene is induced by daunorubicin. FEMS Microbiol Lett 168:243–249

    CAS  PubMed  Google Scholar 

  58. Galm U, Hager MH, Van Lanen SG, Ju J, Thorson JS, Shen B (2005) Antitumor antibiotics: bleomycin, enediynes, and mitomycin. Chem Rev 105:739–758

    CAS  PubMed  Google Scholar 

  59. Galm U, Schimana J, Fiedler H-P, Schmidt J, Li S-M, Heide L (2002) Cloning and analysis of the simocyclinone biosynthetic gene cluster of Streptomyces antibioticus Tü 6040. Arch Microbiol 178:102–114

    CAS  PubMed  Google Scholar 

  60. Gao Q, Thorson JS (2008) The biosynthetic genes encoding for the production of the dynemicin enediyne core in Micromonospora chersina ATCC53710. FEMS Microbiol Lett 282:105–114

    CAS  PubMed  Google Scholar 

  61. García P, Arca P, Suárez JE (1995) Product of fosC, a gene from Pseudomonas syringae, mediates fosfomycin resistance by using ATP as cosubstrate. Antimicrob Agents Chemother 39:1569–1573

    PubMed  Google Scholar 

  62. Gatignol A, Durand H, Tiraby G (1988) Bleomycin resistance conferred by a drug-binding protein. FEBS Lett 230:171–175

    CAS  PubMed  Google Scholar 

  63. Glöckner C, Wolf H (1984) Mechanism of natural resistance to kirromycin-type antibiotics in actinomycetes. FEMS Microbiol Lett 25:121–124

    Google Scholar 

  64. Gourmelen A, Blondelet-Rouault M-H, Pernodet J-L (1998) Characterization of a glycosyl transferase inactivating macrolides, encoded by gimA from Streptomyces ambofaciens. Antimicrob Agents Chemother 42:2612–2619

    CAS  PubMed  Google Scholar 

  65. Graham MY, Weisblum B (1979) 23S ribosomal ribonucleic acid of macrolide-producing streptomycetes contains methylated adenine. J Bacteriol 137:1464–1467

    CAS  PubMed  Google Scholar 

  66. Groβ F, Lewis EA, Piraee M, van Pée K-H, Vining LC, White RL (2002) Isolation of 3′-O-acetylchloramphenicol: a possible intermediate in chloramphenicol biosynthesis. Bioorg Med Chem Lett 12:283–286

    Google Scholar 

  67. Guilfoile PG, Hutchinson CR (1991) A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin. Proc Natl Acad Sci USA 88:8553–8557

    CAS  PubMed  Google Scholar 

  68. Guilfoile PG, Hutchinson CR (1992) The Streptomyces glaucescens TcmR protein represses transcription of the divergently oriented tcmR and tcmA genes by binding to an intergenic operator region. J Bacteriol 174:3659–3666

    CAS  PubMed  Google Scholar 

  69. Guilfoile PG, Hutchinson CR (1992) Sequence and transcriptional analysis of the Streptomyces glaucescens tcmAR tetracenomycin C resistance and repressor gene loci. J Bacteriol 174:3651–3658

    CAS  PubMed  Google Scholar 

  70. Gullón S, Olano C, Abdelfattah MS, Braña AF, Rohr J, Méndez C, Salas JA (2006) Isolation, characterization, and heterologous expression of the biosynthesis gene cluster for the antitumor anthracycline steffimycin. Appl Environ Microbiol 72:4172–4183

    PubMed  Google Scholar 

  71. Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA (2002) The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol Cell 10:117–128

    CAS  PubMed  Google Scholar 

  72. Hara O, Hutchinson CR (1990) Cloning of midecamycin (MLS)-resistance genes from Streptomyces mycarofaciens, Streptomyces lividans and Streptomyces coelicolor A3(2). J Antibiot 43:977–991

    CAS  PubMed  Google Scholar 

  73. Haupt I, Thrum H (1985) Bacterial resistance to streptothricins. J Basic Microbiol 5:335–339

    Google Scholar 

  74. He H, Ding Y, Bartlam M, Sun F, Le Y, Qin X, Tang H, Zhang R, Joachimiak A, Liu J, Zhao N, Rao Z (2003) Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for β-lactam acetylation. J Mol Biol 325:1019–1030

    CAS  PubMed  Google Scholar 

  75. He J, Magarvey N, Piraee M, Vining LC (2001) The gene cluster for chloramphenicol biosynthesis in Streptomyces venezuelae ISP5230 includes novel shikimate pathway homologues and a monomodular non-ribosomal peptide synthetase gene. Microbiology 147:2817–2829

    CAS  PubMed  Google Scholar 

  76. Heinzel P, Werbitzky O, Distler J, Piepersberg W (1988) A second streptomycin resistance gene from Streptomyces griseus codes for streptomycin-3″-phosphotransferase. Relationships between antibiotic and protein kinases. Arch Microbiol 150:184–192

    CAS  PubMed  Google Scholar 

  77. Hillen W, Berens C (1994) Mechanisms underlying expression of Tn10 encoded tetracycline resistance. Annu Rev Microbiol 48:345–369

    CAS  PubMed  Google Scholar 

  78. Hobden AN, Cundliffe E (1980) Ribosomal resistance to the 12,13-epoxytrichothecene antibiotics in the producing organism Myrothecium verrucaria. Biochem J 190:765–770

    CAS  PubMed  Google Scholar 

  79. Holmes DJ, Drocourt D, Tiraby G, Cundliffe E (1991) Cloning of an aminoglycoside-resistance-encoding gene, kamC, from Saccharopolyspora hirsuta: comparison with kamB from Streptomyces tenebrarius. Gene 102:19–26

    CAS  PubMed  Google Scholar 

  80. Horinouchi S, Furuya K, Nishiyama M, Suzuki H, Beppu T (1987) Nucleotide sequence of the streptothricin acetyltransferase gene from Streptomyces lavendulae and its expression in heterologous hosts. J Bacteriol 169:1929–1937

    CAS  PubMed  Google Scholar 

  81. Hotta K, Ishikawa J, Ogata T, Mizuno S (1992) Secondary aminoglycoside resistance in aminoglycoside-producing strains of Streptomyces. Gene 115:113–117

    CAS  PubMed  Google Scholar 

  82. Hughes J, Mellows G, Soughton S (1980) How does Pseudomonas fluorescens, the producing organism of the antibiotic pseudomonic acid A, avoid suicide? FEBS Lett 122:322–324

    CAS  PubMed  Google Scholar 

  83. Iglesias M, Ballesta JPG (1994) Mechanism of resistance to the antibiotic trichothecin in the producing fungi. Eur J Biochem 223:447–453

    CAS  PubMed  Google Scholar 

  84. Imai S, Seto H, Sasaki T, Tsuruoka T, Ogawa H, Satoh A, Inouye S, Niida T, Otake N (1985) Studies on the biosynthesis of bialaphos (SF-1293). 6. Production of N-acetyl-demethylphosphinothricin and N-acetylbialaphos by blocked mutants of Streptomyces hygroscopicus SF-1293 and their roles in the biosynthesis of bialaphos. J Antibiot 38:687–690

    CAS  PubMed  Google Scholar 

  85. Inouye M, Morohoshi T, Horinouchi S, Beppu T (1994) Cloning and sequences of two macrolide-resistance-encoding genes from mycinamicin-producing Micromonospora griseorubida. Gene 141:39–46

    CAS  PubMed  Google Scholar 

  86. Jensen SE, Paradkar AS (1999) Biosynthesis and molecular genetics of clavulanic acid. Antonie Van Leeuwenhoek 75:125–133

    CAS  PubMed  Google Scholar 

  87. Jensen SE, Paradkar AS, Mosher RH, Anders C, Beatty PH, Brumlik MJ, Griffin A, Barton B (2004) Five additional genes are involved in clavulanic acid biosynthesis in Streptomyces clavuligerus. Antimicrob Agents Chemother 48:192–202

    CAS  PubMed  Google Scholar 

  88. Johnson BC, Preston JF III (1980) α-Amanitin-resistant RNA polymerase II from carpophores of Amanita species accumulating amatoxins. Biochim Biophys Acta 607:102–114

    CAS  PubMed  Google Scholar 

  89. Karray F, Darbon E, Oestreicher N, Dominguez H, Tuphile K, Gagnat J, Blondelet-Rouault M-H, Gerbaud C, Pernodet J-L (2007) Organization of the biosynthetic gene cluster for the macrolide antibiotic spiramycin in Streptomyces ambofaciens. Microbiology 153:4111–4122

    CAS  PubMed  Google Scholar 

  90. Kaur P, Russell J (1998) Biochemical coupling between the DrrA and DrrB proteins of the doxorubicin efflux pump of Streptomyces peucetius. J Biol Chem 273:17933–17939

    CAS  PubMed  Google Scholar 

  91. Kawaguchi A, Tomoda H, Okuda S, Awaya J, Ōmura S (1979) Cerulenin resistance in a cerulenin-producing fungus. Isolation of cerulenin-insensitive fatty acyl synthetase. Arch Biochem Biophys 197:30–35

    CAS  PubMed  Google Scholar 

  92. Keeratipibul S, Sugiyama M, Nomi R (1983) Mechanism of resistance to streptothricin of a producing microorganism. Biotechnol Lett 5:441–446

    CAS  Google Scholar 

  93. Kelemen GH, Cundliffe E, Financsek I (1991) Cloning and characterization of gentamicin-resistance genes from Micromonospora purpurea and Micromonospora rosea. Gene 98:53–60

    CAS  PubMed  Google Scholar 

  94. Kelly WL, Pan L, Li C (2009) Thiostrepton biosynthesis: prototype for a new family of bacteriocins. J Am Chem Soc 131:4327–4334

    CAS  PubMed  Google Scholar 

  95. Kharel MK, Subba B, Basnet DB, Woo JS, Lee HC, Liou K, Sohng JK (2004) A gene cluster for biosynthesis of kanamycin from Streptomyces kanamyceticus: comparison with gentamicin biosynthetic gene cluster. Arch Biochem Biophys 429:204–214

    CAS  PubMed  Google Scholar 

  96. Kim CH, Otake N, Yonehara H (1974) Studies on mikamycin B lactonase. I. Degradation of mikamycin B by Streptomyces mitakaensis. J Antibiot 27:903–908

    CAS  PubMed  Google Scholar 

  97. Kimura M, Kaneko I, Komiyama M, Takatsuki A, Koshino H, Yoneyama K, Yamaguchi I (1998) Trichothecene 3-O-acetyltransferase protects both the producing organism and transformed yeast from related mycotoxins. J Biol Chem 273:1654–1661

    CAS  PubMed  Google Scholar 

  98. Kinscherf TG, Coleman RH, Barta TM, Willis DK (1991) Cloning and expression of the tabtoxin biosynthetic region from Pseudomonas syringae. J Bacteriol 173:4124–4132

    CAS  PubMed  Google Scholar 

  99. Kinscherf TG, Willis DK (2005) The biosynthetic gene cluster for the β-lactam antibiotic tabtoxin in Pseudomonas syringae. J Antibiot 58:817–821

    CAS  PubMed  Google Scholar 

  100. Knight TJ, Durbin RD, Langston-Unkefer PJ (1987) Self-protection of Pseudomonas syringae pv. “tabaci” from its toxin, tabtoxinine-β-lactam. J Bacteriol 169:1954–1959

    CAS  PubMed  Google Scholar 

  101. Kobayashi S, Kuzuyama T, Seto H (2000) Characterization of the fomA and fomB gene products from Streptomyces wedmorensis, which confer fosfomycin resistance on Escherichia coli. Antimicrob Agents Chemother 44:647–650

    CAS  PubMed  Google Scholar 

  102. Kojima M, Ezaki N, Amano S, Inouye S, Niida T (1975) Bioconversion of ribostamycin (SF-733). II. Isolation and structure of 3-N-acetylribostamycin, a microbiologically inactive product of ribostamycin produced by Streptomyces ribosidificus. J Antibiot 28:42–47

    CAS  PubMed  Google Scholar 

  103. Kojima M, Inouye S, Niida T (1973) Bioconversion of ribostamycin (SF-733). I. Isolation and structure of 3 (or 1)-N-carboxymethylribostamycin. J Antibiot 26:246–248

    CAS  PubMed  Google Scholar 

  104. Kraiczy P, Haase U, Gencic S, Flindt S, Anke T, Brandt U, Von Jagow G (1996) The molecular basis for the natural resistance of the cytochrome bc1 complex from strobilurin-producing basidiomycetes to center QP inhibitors. Eur J Biochem 235:54–63

    CAS  PubMed  Google Scholar 

  105. Krügel H, Fiedler G, Haupt I, Sarfert E, Simon H (1988) Analysis of the nourseothricin-resistance gene (nat) of Streptomyces noursei. Gene 62:209–217

    PubMed  Google Scholar 

  106. Kuo M-S, Chirby DG, Argoudelis AD, Cialdella JI, Coats JH, Marshall VP (1989) Microbial glycosylation of erythromycin A. Antimicrob Agents Chemother 33:2089–2091

    CAS  PubMed  Google Scholar 

  107. Kuo MS, Yurek DA, Chirby DG, Cialdella JI, Marshall VP (1991) Microbial O-carbamylation of novobiocin. J Antibiot 44:1096–1100

    CAS  PubMed  Google Scholar 

  108. Kuzuyama T, Kobayashi S, O’Hara K, Hidaka T, Seto H (1996) Fosfomycin monophosphate and fosfomycin diphosphate, two inactivated fosfomycin derivatives formed by gene products of fomA and fomB from a fosfomycin producing organism Streptomyces wedmorensis. J Antibiot 49:502–504

    CAS  PubMed  Google Scholar 

  109. Lacalle RA, Tercero JA, Jiménez A (1992) Cloning of the complete biosynthetic gene cluster for an aminonucleoside antibiotic, puromycin, and its regulated expression in heterologous hosts. EMBO J 11:785–792

    CAS  PubMed  Google Scholar 

  110. Le TBK, Fiedler H-P, den Hengst CD, Ahn SK, Maxwell A, Buttner MJ (2009) Coupling of the biosynthesis and export of the DNA gyrase inhibitor simocyclinone in Streptomyces antibioticus. Mol Microbiol 72:1462–1474

    CAS  PubMed  Google Scholar 

  111. Leboul J, Davies J (1982) Enzymatic modification of hygromycin B in Streptomyces hygroscopicus. J Antibiot 35:527–528

    CAS  PubMed  Google Scholar 

  112. Lee C-K, Kamitani Y, Nihira T, Yamada Y (1999) Identification and in vivo functional analysis of a virginiamycin S resistance gene (varS) from Streptomyces virginiae. J Bacteriol 181:3293–3297

    CAS  PubMed  Google Scholar 

  113. Lee C-K, Minami M, Sakuda S, Nihira T, Yamada Y (1996) Stereospecific reduction of virginiamycin M1 as the virginiamycin resistance pathway in Streptomyces virginiae. Antimicrob Agents Chemother 40:595–601

    PubMed  Google Scholar 

  114. Lee SW, Mitchell DA, Markley AL, Hensler ME, Gonzalez D, Wohlrab A, Dorrestein PC, Nizet V, Dixon JE (2008) Discovery of a widely distributed toxin biosynthetic gene cluster. Proc Natl Acad Sci USA 105:5879–5884

    CAS  PubMed  Google Scholar 

  115. Lesnik U, Gormand A, Magdevska V, Fujs S, Raspor P, Hunter I, Petkovic H (2009) Regulatory elements in tetracycline-encoding gene clusters: the otcG gene positively regulates the production of oxytetracycline in Streptomyces rimosus. Food Technol Biotechnol 47:323–330

    CAS  Google Scholar 

  116. Li R, Khaleeli N, Townsend CA (2000) Expansion of the clavulanic acid gene cluster: Identification and in vivo functional analysis of three new genes required for biosynthesis of clavulanic acid by Streptomyces clavuligerus. J Bacteriol 182:4087–4095

    CAS  PubMed  Google Scholar 

  117. Li T-L, Huang F, Haydock SF, Mironenko T, Leadlay PF, Spencer JB (2004) Biosynthetic gene cluster of the glycopeptide antibiotic teicoplanin: characterization of two glycosyltransferases and the key acyltransferase. Chem Biol 11:107–119

    CAS  PubMed  Google Scholar 

  118. Liao R, Duan L, Lei C, Pan H, Ding Y, Zhang Q, Chen D, Shen B, Yu Y, Liu W (2009) Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. Chem Biol 16:141–147

    CAS  PubMed  Google Scholar 

  119. Linton KJ, Cooper HN, Hunter IS, Leadlay PF (1994) An ABC transporter from Streptomyces longisporoflavus confers resistance to the polyether-ionophore antibiotic tetronasin. Mol Microbiol 11:777–785

    CAS  PubMed  Google Scholar 

  120. Liras P (1999) Biosynthesis and molecular genetics of cephamycins. Antonie Van Leeuwenhoek 75:109–124

    CAS  PubMed  Google Scholar 

  121. Liu J (1994) Microcin B17: posttranslational modifications and their biological implications. Proc Natl Acad Sci USA 91:4618–4620

    CAS  PubMed  Google Scholar 

  122. Liu M, Douthwaite S (2002) Resistance to the macrolide antibiotic tylosin is conferred by single methylations at 23S rRNA nucleotides G748 and A2058 acting in synergy. Proc Natl Acad Sci USA 99:14658–14663

    CAS  PubMed  Google Scholar 

  123. Liu W, Christenson SD, Standage S, Shen B (2002) Biosynthesis of the enediyne antitumor antibiotic C-1027. Science 297:1170–1173

    CAS  PubMed  Google Scholar 

  124. Liu W, Nonaka K, Nie L, Zhang J, Christenson SD, Bae J, Van Lanen SG, Zazopoulos E, Farnet CM, Yang CF, Shen B (2005) The neocarzinostatin biosynthetic gene cluster from Streptomyces neocarzinostaticus ATCC 15944 involving two iterative type I polyketide synthases. Chem Biol 12:293–302

    CAS  PubMed  Google Scholar 

  125. Lomovskaya N, Hong S-K, Kim S-U, Fonstein L, Furuya K, Hutchinson CR (1996) The Streptomyces peucetius drrC gene encodes a UvrA-like protein involved in daunorubicin resistance and production. J Bacteriol 178:3238–3245

    CAS  PubMed  Google Scholar 

  126. López-López K, Hernández-Flores JL, Cruz-Aguilar M, Alvarez-Morales A (2004) In Pseudomonas syringae pv. phaseolicola, expression of the argK gene, encoding the phaseolotoxin-resistant ornithine carbamoyltransferase, is regulated indirectly by temperature and directly by a precursor resembling carbamoylphosphate. J Bacteriol 186:146–153

    PubMed  Google Scholar 

  127. Lyutzkanova D, Distler J, Altenbuchner J (1997) A spectinomycin resistance determinant from the spectinomycin producer Streptomyces flavopersicus. Microbiology 143:2135–2143

    CAS  PubMed  Google Scholar 

  128. Malpartida F, Hopwood DA (1984) Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host. Nature 309:462–464

    CAS  PubMed  Google Scholar 

  129. Manavathu EK, Hiratsuka K, Taylor DE (1988) Nucleotide sequence analysis and expression of a tetracycline-resistance gene from Campylobacter jejuni. Gene 62:17–26

    CAS  PubMed  Google Scholar 

  130. Mansouri K, Piepersberg W (1991) Genetics of streptomycin production in Streptomyces griseus: nucleotide sequence of five genes, strFGHIK, including a phosphatase gene. Mol Gen Genet 228:459–469

    CAS  PubMed  Google Scholar 

  131. Marshall CG, Broadhead G, Leskiw BK, Wright GD (1997) d-Ala-d-Ala ligases from glycopeptide antibiotic-producing organisms are highly homologous to the enterococcal vancomycin-resistance ligases VanA and VanB. Proc Natl Acad Sci USA 94:6480–6483

    CAS  PubMed  Google Scholar 

  132. Marshall CG, Lessard IAD, Park I-S, Wright GD (1998) Glycopeptide antibiotic resistance genes in glycopeptide-producing organisms. Antimicrob Agents Chemother 42:2215–2220

    CAS  PubMed  Google Scholar 

  133. Marshall CG, Wright GD (1997) The glycopeptide antibiotic producer Streptomyces toyocaensis NRRL 15009 has both d-alanyl-d-alanine and d-alanyl-d-lactate ligases. FEMS Microbiol Lett 157:295–299

    Article  CAS  PubMed  Google Scholar 

  134. Martin P, Trieu-Cuot P, Courvalin P (1986) Nucleotide sequence of the tetM tetracycline resistance determinant of the streptococcal conjugative shuttle transposon Tn1545. Nucleic Acids Res 14:7047–7058

    CAS  PubMed  Google Scholar 

  135. Matkovic B, Piendl W, Böck A (1984) Ribosomal resistance as a widespread self-defence mechanism in aminoglycoside-producing Micromonospora species. FEMS Microbiol Lett 24:273–276

    CAS  Google Scholar 

  136. Matsuhashi Y, Murakami T, Nojiri C, Toyama H, Anzai H, Nagaoka K (1985) Mechanisms of aminoglycoside-resistance of Streptomyces harboring resistant genes obtained from antibiotic-producers. J Antibiot 38:279–282

    CAS  PubMed  Google Scholar 

  137. Maurer K-H, Pfeiffer F, Zehenderj H, Mecke D (1983) Characterization of two glyceraldehyde-3-phosphate dehydrogenase isoenzymes from the pentalenolactone producer Streptomyces arenae. J Bacteriol 153:930–936

    CAS  PubMed  Google Scholar 

  138. Maxwell A (1997) DNA gyrase as a drug target. Trends Microbiol 5:102–109

    CAS  PubMed  Google Scholar 

  139. McAuliffe O, Ross RP, Hill C (2001) Lantibiotics: structure, biosynthesis and mode of action. FEMS Microbiol Rev 25:285–308

    CAS  PubMed  Google Scholar 

  140. Mellado E, Lorenzana LM, Rodríguez-Sáiz M, Díez B, Liras P, Barredo JL (2002) The clavulanic acid biosynthetic cluster of Streptomyces clavuligerus: genetic organization of the region upstream of the car gene. Microbiology 148:1427–1438

    CAS  PubMed  Google Scholar 

  141. Menéndez N, Braña AF, Salas JA, Méndez C (2007) Involvement of a chromomycin ABC transporter system in secretion of a deacetylated precursor during chromomycin biosynthesis. Microbiology 153:3061–3070

    PubMed  Google Scholar 

  142. Menéndez N, Nur-e-Alam M, Braña AF, Rohr J, Salas JA, Méndez C (2004) Biosynthesis of the antitumor chromomycin A3 in Streptomyces griseus: analysis of the gene cluster and rational design of novel chromomycin analogs. Chem Biol 11:21–32

    PubMed  Google Scholar 

  143. Menéndez N, Nur-e-Alam M, Braña AF, Rohr J, Salas JA, Méndez C (2004) Tailoring modification of deoxysugars during biosynthesis of the antitumour drug chromomycin A3 by Streptomyces griseus ssp. griseus. Mol Microbiol 53:903–915

    PubMed  Google Scholar 

  144. Menzel R, Gellert M (1983) Regulation of the genes for E.coli DNA gyrase: homeostatic control of DNA supercoiling. Cell 34:105–113

    CAS  PubMed  Google Scholar 

  145. Mikulik K, Weiser J, Haskova D (1982) Protein synthesis elongation factor EFTu from Streptomyces collinus producing kirromycin. Biochem Biophys Res Commun 108:861–867

    CAS  PubMed  Google Scholar 

  146. Miller AL, Walker JB (1969) Enzymatic phosphorylation of streptomycin by extracts of streptomycin-producing strains of Streptomyces. J Bacteriol 99:401–405

    CAS  PubMed  Google Scholar 

  147. Mitchell JI, Logan PG, Cushing KE, Ritchie DA (1990) Novobiocin-resistance sequences from the novobiocin-producing strain Streptomyces niveus. Mol Microbiol 4:845–849

    CAS  PubMed  Google Scholar 

  148. Mitchell RE, Bieleski RL (1977) Involvement of phaseolotoxin in halo blight of beans. Transport and conversion to functional toxin. Plant Physiol 60:723–729

    CAS  PubMed  Google Scholar 

  149. Miyashiro S, Ando T, Hirayama K, Kida T, Shibai H, Murai A, Shiio T, Udaka S (1983) New streptothricin-group antibiotics, AN201 I and II. Screening, fermentation, isolation, structure and biological activity. J Antibiot 36:1638–1643

    CAS  PubMed  Google Scholar 

  150. Möhrle VG, Tieleman LN, Kraal B (1997) Elongation factor Tu1 of the antibiotic GE2270A producer Planobispora rosea has an unexpected resistance profile against EF-Tu targeted antibiotics. Biochem Biophys Res Commun 230:320–326

    PubMed  Google Scholar 

  151. Moore RE, Niemczura WP, Kwok OCH, Patil SS (1984) Inhibitors of ornithine carbamoyltransferase from Pseudomonas syringae pv. phaseolicola. Revised structure of phaseolotoxin. Tetrahedron Lett 25:3931–3934

    CAS  Google Scholar 

  152. Mootz HD, Marahiel MA (1997) The tyrocidine biosynthesis operon of Bacillus brevis: complete nucleotide sequence and biochemical characterization of functional internal adenylation domains. J Bacteriol 179:6843–6850

    CAS  PubMed  Google Scholar 

  153. Mosher RH, Camp DJ, Yang K, Brown MP, Shaw WV, Vining LC (1995) Inactivation of chloramphenicol by O-phosphorylation. A novel resistance mechanism in Streptomyces venezuelae ISP5230, a chloramphenicol producer. J Biol Chem 270:27000–27006

    CAS  PubMed  Google Scholar 

  154. Mosher RH, Ranade NP, Schrempf H, Vining LC (1990) Chloramphenicol resistance in Streptomyces: cloning and characterization of a chloramphenicol hydrolase gene from Streptomyces venezuelae. J Gen Microbiol 136:293–301

    CAS  PubMed  Google Scholar 

  155. Nakano MM, Mashiko H, Ogawara H (1984) Cloning of the kanamycin resistance gene from a kanamycin-producing Streptomyces species. J Bacteriol 157:79–83

    CAS  PubMed  Google Scholar 

  156. Nimi O, Ito G, Sueda S, Nomi R (1971) Phosphorylation of streptomycin at C6-OH of streptidine moiety by an intracellular enzyme of Streptomyces griseus. Agric Biol Chem 35:848–855

    CAS  Google Scholar 

  157. Ogawara H (1981) Antibiotic resistance in pathogenic and producing bacteria, with special reference to β-lactam antibiotics. Microbiol Rev 45:591–619

    CAS  PubMed  Google Scholar 

  158. O’Hara K, Kanda T, Kono M (1988) Structure of a phosphorylated derivative of oleandomycin, obtained by reaction of oleandomycin with an extract of an erythromycin-resistant strain of Escherichia coli. J Antibiot 41:823–827

    PubMed  Google Scholar 

  159. Ohnuki T, Imanaka T, Aiba S (1985) Self-cloning in Streptomyces griseus of an str gene cluster for streptomycin biosynthesis and streptomycin resistance. J Bacteriol 164:85–94

    CAS  PubMed  Google Scholar 

  160. Ohnuki T, Katoh T, Imanaka T, Aiba S (1985) Molecular cloning of tetracycline resistance genes from Streptomyces rimosus in Streptomyces griseus and characterization of the cloned genes. J Bacteriol 161:1010–1016

    CAS  PubMed  Google Scholar 

  161. Ohta T, Dairi T, Hasegawa M (1993) Characterization of two different types of resistance genes among producers of fortimicin-group antibiotics. J Gen Microbiol 139:591–599

    CAS  PubMed  Google Scholar 

  162. Ohta T, Hasegawa M (1993) Analysis of the nucleotide sequence of fmrT encoding the self-defense gene of the istamycin producer, Streptomyces tenjimariensis ATCC 31602; comparison with the sequences of kamB of Streptomyces tenebrarius NCIB 11028 and kamC of Saccharopolyspora hirsuta CL102. J Antibiot 46:511–517

  163. Ohta T, Hasegawa M (1993) Analysis of the self-defense gene (fmrO) of a fortimicin A (astromicin) producer, Micromonospora olivasterospora: comparison with other aminoglycoside-resistance-encoding genes. Gene 127:63–69

    CAS  PubMed  Google Scholar 

  164. Olano C, Rodríguez AM, Méndez C, Salas JA (1995) A second ABC transporter is involved in oleandomycin resistance and its secretion by Streptomyces antibioticus. Mol Microbiol 16:333–343

    CAS  PubMed  Google Scholar 

  165. Oliynyk M, Stark CBW, Bhatt A, Jones MA, Hughes-Thomas ZA, Wilkinson C, Oliynyk Z, Demydchuk Y, Staunton J, Leadlay PF (2003) Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization. Mol Microbiol 49:1179–1190

    CAS  PubMed  Google Scholar 

  166. Olsthoorn-Tieleman LN, Fischer SEJ, Kraal B (2002) The unique tuf2 gene from the kirromycin producer Streptomyces ramocissimus encodes a minor and kirromycin-sensitive elongation factor Tu. J Bacteriol 184:4211–4218

    CAS  PubMed  Google Scholar 

  167. Olsthoorn-Tieleman LN, Palstra R-JTS, van Wezel GP, Bibb MJ, Pleij CWA (2007) Elongation factor Tu3 (EF-Tu3) from the kirrromycin producer Streptomyces ramocissimus is resistant to three classes of EF-Tu-specific inhibitors. J Bacteriol 189:3581–3590

    CAS  PubMed  Google Scholar 

  168. Paradkar AS, Aidoo KA, Wong A, Jensen SE (1996) Molecular analysis of a β-lactam resistance gene encoded within the cephamycin gene cluster of Streptomyces clavuligerus. J Bacteriol 178:6266–6274

    CAS  PubMed  Google Scholar 

  169. Pardo JM, Malpartida F, Rico M, Jiménez A (1985) Biochemical basis of resistance to hygromycin B in Streptomyces hygroscopicus–the producing organism. J Gen Microbiol 131:1289–1298

    CAS  PubMed  Google Scholar 

  170. Peet RC, Panopoulos NJ (1987) Ornithine carbamoyltransferase genes and phaseolotoxin immunity in Pseudomonas syringae pv. phaseolicola. EMBO J 6:3585–3591

    CAS  PubMed  Google Scholar 

  171. Pelzer S, Süβmuth R, Heckmann D, Recktenwald J, Huber P, Jung G, Wohlleben W (1999) Identification and analysis of the balhimycin biosynthetic gene cluster and its use for manipulating glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908. Antimicrob Agents Chemother 43:1565–1573

    CAS  PubMed  Google Scholar 

  172. Pérez-González JA, López-Cabrera M, Pardo JM, Jiménez A (1989) Biochemical characterization of two cloned resistance determinants encoding a paromomycin acetyltransferase and a paromomycin phosphotransferase from Streptomyces rimosus forma paromomycinus. J Bacteriol 171:329–334

    PubMed  Google Scholar 

  173. Pérez-González JA, Vara J, Jiménez A (1983) Acetylation of puromycin by Streptomyces alboniger the producing organism. Biochem Biophys Res Commun 113:772–777

    PubMed  Google Scholar 

  174. Pérez-Llarena FJ, Rodríguez-García A, Enguita FJ, Martín JF, Liras P (1998) The pcd gene encoding piperideine-6-carboxylate dehydrogenase involved in biosynthesis of α-aminoadipic acid is located in the cephamycin cluster of Streptomyces clavuligerus. J Bacteriol 180:4753–4756

    PubMed  Google Scholar 

  175. Pernodet J-L, Alegre M-T, Blondelet-Rouault M-H, Guérineau M (1993) Resistance to spiramycin in Streptomyces ambofaciens, the producer organism, involves at least two different mechanisms. J Gen Microbiol 139:1003–1011

    CAS  PubMed  Google Scholar 

  176. Pernodet J-L, Fish S, Blondelet-Rouault M-H, Cundliffe E (1996) The macrolide-lincosamide-streptogramin B resistance phenotypes characterized by using a specifically deleted, antibiotic-sensitive strain of Streptomyces lividans. Antimicrob Agents Chemother 40:581–585

    CAS  PubMed  Google Scholar 

  177. Pernodet J-L, Gourmelen A, Blondelet-Rouault M-H, Cundliffe E (1999) Dispensable ribosomal resistance to spiramycin conferred by srmA in the spiramycin producer Streptomyces ambofaciens. Microbiology 145:2355–2364

    CAS  PubMed  Google Scholar 

  178. Peschke U, Schmidt H, Zhang H-Z, Piepersberg W (1995) Molecular characterization of the lincomycin-production gene cluster of Streptomyces lincolnensis 78–11. Mol Microbiol 16:1137–1156

    CAS  PubMed  Google Scholar 

  179. Piendl W, Böck A (1982) Ribosomal resistance in the gentamicin producer organism Micromonospora purpurea. Antimicrob Agents Chemother 22:231–236

    CAS  PubMed  Google Scholar 

  180. Plater R, Robinson JA (1992) Cloning and sequence of a gene encoding macrotetrolide antibiotic resistance from Streptomyces griseus. Gene 112:117–122

    CAS  PubMed  Google Scholar 

  181. Podlesek Z, Comino A, Herzog-Velikonja B, Grabnar M (2000) The role of the bacitracin ABC transporter in bacitracin resistance and collateral detergent sensitivity. FEMS Microbiol Lett 188:103–106

    CAS  PubMed  Google Scholar 

  182. Pojer F, Li S-M, Heide L (2002) Molecular cloning and sequence analysis of the clorobiocin biosynthetic gene cluster: new insights into the biosynthesis of aminocoumarin antibiotics. Microbiology 148:3901–3911

    CAS  PubMed  Google Scholar 

  183. Pootoolal J, Thomas MG, Marshall CG, Neu JM, Hubbard BK, Walsh CT, Wright GD (2002) Assembling the glycopeptide antibiotic scaffold: the biosynthesis of A47934 from Streptomyces toyocaensis NRRL 15009. Proc Natl Acad Sci USA 99:8962–8967

    CAS  PubMed  Google Scholar 

  184. Porse BT, Cundliffe E, Garrett RA (1999) The antibiotic micrococcin acts on protein L11 at the ribosomal GTPase centre. J Mol Biol 287:33–45

    CAS  PubMed  Google Scholar 

  185. Pulsawat N, Kitani S, Nihira T (2007) Characterization of biosynthetic gene cluster for the production of virginiamycin M, a streptogramin type A antibiotic, in Streptomyces virginiae. Gene 393:31–42

    CAS  PubMed  Google Scholar 

  186. Quirós LM, Aguirrezabalaga I, Olano C, Méndez C, Salas JA (1998) Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus. Mol Microbiol 28:1177–1185

    PubMed  Google Scholar 

  187. Quirós LM, Hernández C, Salas JA (1994) Purification and characterization of an extracellular enzyme from Streptomyces antibioticus that converts inactive glycosylated oleandomycin into the active antibiotic. Eur J Biochem 222:129–135

    PubMed  Google Scholar 

  188. Ramos A, Lombó F, Braña AF, Rohr J, Méndez C, Salas JA (2008) Biosynthesis of elloramycin in Streptomyces olivaceus requires glycosylation by enzymes encoded outside the aglycon cluster. Microbiology 154:781–788

    CAS  PubMed  Google Scholar 

  189. Recktenwald J, Shawky R, Puk O, Pfennig F, Keller U, Wohlleben W, Pelzer S (2002) Nonribosomal biosynthesis of vancomycin-type antibiotics: a heptapeptide backbone and eight peptide synthetase modules. Microbiology 148:1105–1118

    CAS  PubMed  Google Scholar 

  190. Roberts MC (1994) Epidemiology of tetracycline-resistance determinants. Trends Microbiol 2:353–357

    CAS  PubMed  Google Scholar 

  191. Roberts MC, Sutcliffe J, Courvalin P, Jensen LB, Rood J, Seppala H (1999) Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob Agents Chemother 43:2823–2830

    CAS  PubMed  Google Scholar 

  192. Rokem JS, Hurley LH (1981) Sensitivity and permeability of the anthramycin producing organism Streptomyces refuineus to anthramycin and structurally related antibiotics. J Antibiot 34:1171–1174

    CAS  PubMed  Google Scholar 

  193. Rosteck PR Jr, Reynolds PA, Hershberger CL (1991) Homology between proteins controlling Streptomyces fradiae tylosin resistance and ATP-binding transport. Gene 102:27–32

    CAS  PubMed  Google Scholar 

  194. Rowley KB, Xu R, Patil SS (2000) Molecular analysis of thermoregulation of phaseolotoxin-resistant ornithine carbamoyltransferase (argK) from Pseudomonas syringae pv. phaseolicola. Mol Plant-Microbe Interact 13:1071–1080

    CAS  PubMed  Google Scholar 

  195. Roza J, Blanco MG, Hardisson C, Salas JA (1986) Self-resistance in actinomycetes producing inhibitors of RNA polymerase. J Antibiot 39:609–612

    CAS  PubMed  Google Scholar 

  196. Sahl H-G, Bierbaum G (1998) Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from Gram-positive bacteria. Annu Rev Microbiol 52:41–79

    CAS  PubMed  Google Scholar 

  197. Salah-Bey K, Blanc V, Thompson CJ (1995) Stress-activated expression of a Streptomyces pristinaespiralis multidrug resistance gene (ptr) in various Streptomyces spp. and Escherichia coli. Mol Microbiol 17:1001–1012

    CAS  PubMed  Google Scholar 

  198. Sanchez-Pescador R, Brown JT, Roberts M, Urdea MS (1988) Homology of the TetM with translational elongation factors: implications for potential modes of tetM conferred tetracycline resistance. Nucleic Acids Res 16:1218

    CAS  PubMed  Google Scholar 

  199. Savic M, Lovric J, Tomic TI, Vasiljevic B, Conn GL (2009) Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics. Nucleic Acids Res 37:5420–5431

    CAS  PubMed  Google Scholar 

  200. Schlünzen F, Zarivach R, Harms J, Bashan A, Tocilj A, Albrecht R, Yonath A, Franceschi F (2001) Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature 413:814–821

    PubMed  Google Scholar 

  201. Schmutz E, Hennig S, Li S-M, Heide L (2004) Identification of a topoisomerase IV in actinobacteria: purification and characterization of ParYR and GyrBR from the coumermycin A1 producer Streptomyces rishiriensis DSM 40489. Microbiology 150:641–647

    CAS  PubMed  Google Scholar 

  202. Schmutz E, Mühlenweg A, Li S-M, Heide L (2003) Resistance genes of aminocoumarin producers: two type II topoisomerase genes confer resistance against coumermycin A1 and clorobiocin. Antimicrob Agents Chemother 47:869–877

    CAS  PubMed  Google Scholar 

  203. Schoner B, Geistlich M, Rosteck P Jr, Rao RN, Seno E, Reynolds P, Cox K, Burgett S, Hershberger C (1992) Sequence similarity between macrolide-resistance determinants and ATP-binding proteins. Gene 115:93–96

    CAS  PubMed  Google Scholar 

  204. Sheldon PJ, Johnson DA, August PR, Liu H-W, Sherman DH (1997) Characterization of a mitomycin-binding drug resistance mechanism from the producing organism, Streptomyces lavendulae. J Bacteriol 179:1796–1804

    CAS  PubMed  Google Scholar 

  205. Sheldon PJ, Mao Y, He M, Sherman DH (1999) Mitomycin resistance in Streptomyces lavendulae includes a novel drug-binding-protein-dependent export system. J Bacteriol 181:2507–2512

    CAS  PubMed  Google Scholar 

  206. Shirai M, Aida T (1984) Self-resistance of colistin-producing Bacillus colistinus. II. Effect of colistin on protoplasts and liposomes derived from colistin-producing Bacillus colistinus. Agric Biol Chem 48:857–863

    CAS  Google Scholar 

  207. Skeggs PA, Holmes DJ, Cundliffe E (1987) Cloning of aminoglycoside-resistance determinants from Streptomyces tenebrarius and comparison with related genes from other actinomycetes. J Gen Microbiol 133:915–923

    CAS  PubMed  Google Scholar 

  208. Skeggs PA, Thompson J, Cundliffe E (1985) Methylation of 16S ribosomal RNA and resistance to aminoglycoside antibiotics in clones of Streptomyces lividans carrying DNA from Streptomyces tenjimariensis. Mol Gen Genet 200:415–421

    CAS  PubMed  Google Scholar 

  209. Skinner R, Cundliffe E, Schmidt FJ (1983) Site of action of a ribosomal RNA methylase responsible for resistance to erythromycin and other antibiotics. J Biol Chem 258:12702–12706

    CAS  PubMed  Google Scholar 

  210. Skinner RH, Cundliffe E (1980) Resistance to the antibiotics viomycin and capreomycin in the Streptomyces species which produce them. J Gen Microbiol 120:95–104

    CAS  PubMed  Google Scholar 

  211. Smith TM, Jiang Y-F, Shipley P, Floss HG (1995) The thiostrepton-resistance-encoding gene in Streptomyces laurentii is located within a cluster of ribosomal protein operons. Gene 164:137–142

    CAS  PubMed  Google Scholar 

  212. Sosio M, Amati G, Cappellano C, Sarubbi E, Monti F, Donadio S (1996) An elongation factor Tu (EF-Tu) resistant to the EF-Tu inhibitor GE2270 in the producing organism Planobispora rosea. Mol Microbiol 22:43–51

    CAS  PubMed  Google Scholar 

  213. Sosio M, Kloosterman H, Bianchi A, de Vreugd P, Dijkhuizen L, Donadio S (2004) Organization of the teicoplanin gene cluster in Actinoplanes teichomyceticus. Microbiology 150:95–102

    CAS  PubMed  Google Scholar 

  214. Sosio M, Stinchi S, Beltrametti F, Lazzarini A, Donadio S (2003) The gene cluster for the biosynthesis of the glycopeptide antibiotic A40926 by Nonomuraea species. Chem Biol 10:541–549

    CAS  PubMed  Google Scholar 

  215. Spedding G, Cundliffe E (1984) Identification of the altered ribosomal component responsible for resistance to micrococcin in mutants of Bacillus megaterium. Eur J Biochem 140:453–459

    CAS  PubMed  Google Scholar 

  216. Staskawicz BJ, Panopoulos NJ, Hoogenraad NJ (1980) Phaseolotoxin-insensitive ornithine carbamoyltransferase of Pseudomonas syringae pv. phaseolicola: Basis for immunity to phaseolotoxin. J Bacteriol 142:720–723

    CAS  PubMed  Google Scholar 

  217. Steffensky M, Mühlenweg A, Wang Z-X, Li S-M, Heide L (2000) Identification of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891. Antimicrob Agents Chemother 44:1214–1222

    CAS  PubMed  Google Scholar 

  218. Stein T, Heinzmann S, Solovieva I, Entian K-D (2003) Function of Lactococcus lactis nisin immunity genes nisI and nisFEG after coordinated expression in the surrogate host Bacillus subtilis. J Biol Chem 278:89–94

    CAS  PubMed  Google Scholar 

  219. Strauch E, Wohlleben W, Pühler A (1988) Cloning of a phosphinothricin N-acetyltransferase gene from Streptomyces viridochromogenes Tü494 and its expression in Streptomyces lividans and Escherichia coli. Gene 63:65–74

    CAS  PubMed  Google Scholar 

  220. Sugiyama M, Paik S-Y, Nomi R (1985) Mechanism of self-protection in a puromycin-producing micro-organism. J Gen Microbiol 131:1999–2005

    CAS  PubMed  Google Scholar 

  221. Sugiyama M, Takeda A, Paik S-Y, Nimi O, Nomi R (1986) Acetylation of blasticidin S by its producing actinomycetes. J Antibiot 39:827–832

    CAS  PubMed  Google Scholar 

  222. Sugiyama M, Thompson CJ, Kumagai T, Suzuki K, Deblaere R, Villarroel R, Davies J (1994) Characterisation by molecular cloning of two genes from Streptomyces verticillus encoding resistance to bleomycin. Gene 151:11–16

    CAS  PubMed  Google Scholar 

  223. Sun Y, Zhou X, Dong H, Tu G, Wang M, Wang B, Deng Z (2003) A complete gene cluster from Streptomyces nanchangensis NS3226 encoding biosynthesis of the polyether ionophore nanchangmycin. Chem Biol 10:431–441

    CAS  PubMed  Google Scholar 

  224. Tahlan K, Ahn SK, Sing A, Bodnaruk TD, Willems AR, Davidson AR, Nodwell JR (2007) Initiation of actinorhodin export in Streptomyces coelicolor. Mol Microbiol 63:951–961

    CAS  PubMed  Google Scholar 

  225. Teraoka H, Tanaka K (1974) Properties of ribosomes from Streptomyces erythreus and Streptomyces griseus. J Bacteriol 120:316–321

    CAS  PubMed  Google Scholar 

  226. Tercero JA, Espinosa JC, Lacalle RA, Jiménez A (1996) The biosynthetic pathway of the aminonucleoside antibiotic puromycin, as deduced from the molecular analysis of the pur cluster of Streptomyces alboniger. J Biol Chem 271:1579–1590

    CAS  PubMed  Google Scholar 

  227. Tercero JA, Lacalle RA, Jiménez A (1993) The pur8 gene from the pur cluster of Streptomyces alboniger encodes a highly hydrophobic polypeptide which confers resistance to puromycin. Eur J Biochem 218:963–971

    CAS  PubMed  Google Scholar 

  228. Tetzlaff CN, You Z, Cane DE, Takamatsu S, Omura S, Ikeda H (2006) A gene cluster for biosynthesis of the sesquiterpenoid antibiotic pentalenolactone in Streptomyces avermitilis. Biochemistry 45:6179–6186

    CAS  PubMed  Google Scholar 

  229. Thiara AS, Cundliffe E (1988) Cloning and characterization of a DNA gyrase B gene from Streptomyces sphaeroides that confers resistance to novobiocin. EMBO J 7:2255–2259

    CAS  PubMed  Google Scholar 

  230. Thiara AS, Cundliffe E (1989) Interplay of novobiocin-resistant and -sensitive DNA gyrase activities in self-protection of the novobiocin producer, Streptomyces sphaeroides. Gene 81:65–72

    CAS  PubMed  Google Scholar 

  231. Thiara AS, Cundliffe E (1995) Analysis of two capreomycin-resistance determinants from Streptomyces capreolus and characterization of the action of their products. Gene 167:121–126

    CAS  PubMed  Google Scholar 

  232. Thomas MG, Chan YA, Ozanick SG (2003) Deciphering tuberactinomycin biosynthesis: Isolation, sequencing, and annotation of the viomycin biosynthetic gene cluster. Antimicrob Agents Chemother 47:2823–2830

    CAS  PubMed  Google Scholar 

  233. Thompson CJ, Rao Movva N, Tizard R, Crameri R, Davies JE, Lauwereys M, Botterman J (1987) Characterization of the herbicide-resistance gene bar from Streptomyces hygroscopicus. EMBO J 6:2519–2523

    CAS  PubMed  Google Scholar 

  234. Thompson CJ, Skinner RH, Thompson J, Ward JM, Hopwood DA, Cundliffe E (1982) Biochemical characterization of resistance determinants cloned from antibiotic-producing streptomycetes. J Bacteriol 151:678–685

    CAS  PubMed  Google Scholar 

  235. Thompson J, Cundliffe E (1980) Resistance to thiostrepton, siomycin and sporangiomycin in actinomycetes that produce them. J Bacteriol 142:455–461

    CAS  PubMed  Google Scholar 

  236. Thompson J, Cundliffe E, Stark MJR (1982) The mode of action of berninamycin and the mechanism of resistance in the producing organism, Streptomyces bernensis. J Gen Microbiol 128:875–884

    CAS  PubMed  Google Scholar 

  237. Thompson J, Schmidt F, Cundliffe E (1982) Site of action of a ribosomal RNA methylase conferring resistance to thiostrepton. J Biol Chem 257:7915–7917

    CAS  PubMed  Google Scholar 

  238. Thompson J, Skeggs PA, Cundliffe E (1985) Methylation of 16S ribosomal RNA and resistance to the aminoglycoside antibiotics gentamicin and kanamycin determined by DNA from the gentamicin-producer, Micromonospora purpurea. Mol Gen Genet 201:168–173

    CAS  PubMed  Google Scholar 

  239. Thorson JS, Shen B, Whitwam RE, Liu W, Li Y, Ahlert J (1999) Enediyne biosynthesis and self-resistance: a progress report. Bioorg Chem 27:172–188

    CAS  Google Scholar 

  240. Treede I, Jakobsen L, Kirpekar F, Vester B, Weitnauer G, Bechthold A, Douthwaite S (2003) The avilamycin resistance determinants AviRa and AviRb methylate 23S rRNA at the guanosine 2535 base and the uridine 2479 ribose. Mol Microbiol 49:309–318

    CAS  PubMed  Google Scholar 

  241. Trefzer A, Pelzer S, Schimana J, Stockert S, Bihlmaier C, Fiedler H-P, Welzel K, Vente A, Bechthold A (2002) Biosynthetic gene cluster of simocyclinone, a natural multihybrid antibiotic. Antimicrob Agents Chemother 46:1174–1182

    CAS  PubMed  Google Scholar 

  242. Van Lanen SG, Oh T-j, Liu W, Wendt-Pienkowski E, Shen B (2007) Characterization of the maduropeptin biosynthetic gene cluster from Actinomadura madurae ATCC 39144 supporting a unifying paradigm for enediyne biosynthesis. J Am Chem Soc 129:13082–13094

    PubMed  Google Scholar 

  243. van Wageningen AMA, Kirkpatrick PN, Williams DH, Harris BR, Kershaw JK, Lennard NJ, Jones M, Jones SJM, Solenberg PJ (1998) Sequencing and analysis of genes involved in the biosynthesis of a vancomycin group antibiotic. Chem Biol 5:155–162

    PubMed  Google Scholar 

  244. Vara J, Malpartida F, Hopwood DA, Jiménez A (1985) Cloning and expression of a puromycin N-acetyltransferase gene from Streptomyces alboniger in Streptomyces lividans and Escherichia coli. Gene 33:197–206

    CAS  PubMed  Google Scholar 

  245. Vijgenboom E, Woudt LP, Heinstra PWH, Rietveld K, van Haarlem J, van Wezel GP, Shochat S, Bosch L (1994) Three tuf-like genes in the kirromycin producer Streptomyces ramocissimus. Microbiology 140:983–998

    CAS  PubMed  Google Scholar 

  246. Vilches C, Hernández C, Méndez C, Salas JA (1992) Role of glycosylation and deglycosylation in biosynthesis of and resistance to oleandomycin in the producer organism, Streptomyces antibioticus. J Bacteriol 174:161–165

    CAS  PubMed  Google Scholar 

  247. Vining LC (1979) Antibiotic tolerance in producer organisms. Adv Appl Microbiol 25:147–168

    CAS  PubMed  Google Scholar 

  248. Vögtli M, Hütter R (1987) Characterisation of the hydroxystreptomycin phosphotransferase gene (sph) of Streptomyces glaucescens: Nucleotide sequence and promoter analysis. Mol Gen Genet 208:195–203

    PubMed  Google Scholar 

  249. Walczak RJ, Woo AJ, Strohl WR, Priestley ND (2000) Nonactin biosynthesis: the potential nonactin biosynthesis gene cluster contains type II polyketide synthase-like genes. FEMS Microbiol Lett 183:171–175

    CAS  PubMed  Google Scholar 

  250. Walker JB, Skorvaga M (1973) Phosphorylation of streptomycin and dihydrostreptomycin by Streptomyces. J Biol Chem 248:2435–2440

    CAS  PubMed  Google Scholar 

  251. Walker MS, Walker JB (1970) Streptomycin biosynthesis and metabolism. Enzymatic phosphorylation of dihydrostreptobiosamine moieties of dihydrostreptomycin-(streptidino)phosphate and dihydrostreptomycin by Streptomyces extracts. J Biol Chem 245:6683–6689

    CAS  PubMed  Google Scholar 

  252. Walker MS, Walker JB (1971) Streptomycin biosynthesis. Separation and substrate specificities of phosphatases acting on guanidino-deoxy-scyllo-inositol phosphate and streptomycin-(streptidino) phosphate. J Biol Chem 246:7034–7040

    CAS  PubMed  Google Scholar 

  253. Wang Z-X, Li S-M, Heide L (2000) Identification of the coumermycin A1 biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489. Antimicrob Agents Chemother 44:3040–3048

    CAS  PubMed  Google Scholar 

  254. Weisblum B (1985) Inducible resistance to macrolides, lincosamides and streptogramin type B antibiotics: the resistance phenotype, its biological diversity, and structural elements that regulate expression—a review. J Antimicrob Chemother 16(Suppl A):63–90

    CAS  PubMed  Google Scholar 

  255. Weitnauer G, Gaisser S, Trefzer A, Stockert S, Westrich L, Quirós LM, Méndez C, Salas JA, Bechthold A (2001) An ATP-binding cassette transporter and two rRNA methyltransferases are involved in resistance to avilamycin in the producer organism Streptomyces viridochromogenes Tü57. Antimicrob Agents Chemother 45:690–695

    CAS  PubMed  Google Scholar 

  256. Weitnauer G, Mühlenweg A, Trefzer A, Hoffmeister D, Süßmuth RD, Jung G, Welzel K, Vente A, Girreser U, Bechthold A (2001) Biosynthesis of the orthosomycin antibiotic avilamycin A: deductions from the molecular analysis of the avi biosynthetic gene cluster of Streptomyces viridochromogenes Tü57 and production of new antibiotics. Chem Biol 8:569–581

    CAS  PubMed  Google Scholar 

  257. Wieland Brown LC, Acker MG, Clardy J, Walsh CT, Fischbach MA (2009) Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin. Proc Natl Acad Sci USA 106:2549–2553

    CAS  PubMed  Google Scholar 

  258. Wiley PF, Baczynskyj L, Dolak LA, Cialdella JI, Marshall VP (1987) Enzymatic phosphorylation of macrolide antibiotics. J Antibiot 40:195–201

    CAS  PubMed  Google Scholar 

  259. Wohlleben W, Arnold W, Broer I, Hillemann D, Strauch E, Pühler A (1988) Nucleotide sequence of the phosphinothricin N-acetyltransferase gene from Streptomyces viridochromogenes Tü494 and its expression in Nicotiana tabacum. Gene 70:25–37

    CAS  PubMed  Google Scholar 

  260. Woodyer RD, Shao Z, Thomas PM, Kelleher NL, Blodgett JAV, Metcalf WW, van der Donk WA, Zhao H (2006) Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster. Chem Biol 13:1171–1182

    CAS  PubMed  Google Scholar 

  261. Xue Y, Zhao L, Liu H-w, Sherman DH (1998) A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: architecture of metabolic diversity. Proc Natl Acad Sci USA 95:12111–12116

    CAS  PubMed  Google Scholar 

  262. Yamamoto H, Hotta K, Okami Y, Umezawa H (1981) Ribosomal resistance of an istamycin producer, Streptomyces tenjimariensis, to aminoglycoside antibiotics. Biochem Biophys Res Commun 100:1396–1401

    CAS  PubMed  Google Scholar 

  263. Yamamoto H, Hotta K, Okami Y, Umezawa H (1982) Mechanism of resistance to aminoglycoside antibiotics in nebramycin-producing Streptomyces tenebrarius. J Antibiot 35:1020–1025

    CAS  PubMed  Google Scholar 

  264. Zalacain M, Cundliffe E (1989) Methylation of 23S ribosomal RNA caused by tlrA (ermSF), a tylosin resistance determinant from Streptomyces fradiae. J Bacteriol 171:4254–4260

    CAS  PubMed  Google Scholar 

  265. Zalacain M, Cundliffe E (1990) Methylation of 23S ribosomal RNA due to carB, an antibiotic-resistance determinant from the carbomycin producer, Streptomyces thermotolerans. Eur J Biochem 189:67–72

    CAS  PubMed  Google Scholar 

  266. Zalacain M, Cundliffe E (1991) Cloning of tlrD, a fourth resistance gene, from the tylosin producer, Streptomyces fradiae. Gene 97:137–142

    CAS  PubMed  Google Scholar 

  267. Zalacain M, Pardo JM, Jiménez A (1987) Purification and characterization of a hygromycin B phosphotransferase from Streptomyces hygroscopicus. Eur J Biochem 162:419–422

    CAS  PubMed  Google Scholar 

  268. Zhang H-Z, Schmidt H, Piepersberg W (1992) Molecular cloning and characterization of two lincomycin-resistance genes, lmrA and lmrB, from Streptomyces lincolnensis 78–11. Mol Microbiol 6:2147–2157

    CAS  PubMed  Google Scholar 

  269. Zhang W, Ames BD, Tsai S-C, Tang Y (2006) Engineered biosynthesis of a novel amidated polyketide using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase. Appl Environ Microbiol 72:2573–2580

    CAS  PubMed  Google Scholar 

  270. Zhao L, Sherman DH, Liu H-w (1998) Biosynthesis of desosamine: molecular evidence suggesting β-glucosylation as a self-resistance mechanism in methymycin/neomethymycin producing strain, Streptomyces venezuelae. J Am Chem Soc 120:9374–9375

    CAS  Google Scholar 

Download references

Acknowledgments

We thank innumerable colleagues for enlightenment over the years and offer apologies to those whose work might not be cited here. In preparing this article we were helped and advised by Juan Pedro Ballesta, Dawn Bignell, Mark Buttner, Jean-Luc Pernodet and José Salas. In particular, we value wise counsel from Richard Baltz.

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Leicester, Leicester, LE1 9HN, UK

    Eric Cundliffe

  2. Research Institute for Scientists Emeriti, Drew University, Madison, NJ, 07940, USA

    Arnold L. Demain

Authors
  1. Eric Cundliffe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arnold L. Demain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric Cundliffe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cundliffe, E., Demain, A.L. Avoidance of suicide in antibiotic-producing microbes. J Ind Microbiol Biotechnol 37, 643–672 (2010). https://doi.org/10.1007/s10295-010-0721-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-010-0721-x

Keywords

Search

Navigation