Publikationsserver der Universitätsbibliothek Marburg
Titel:Ribosome-Independent Biosynthesis of Peptide Natural Products: Nonribosomal Peptide Synthetases and Cyclodipeptide Synthases
Autor:Gießen, Tobias
Weitere Beteiligte: Marahiel, Mohamed A. (Prof. Dr.)
Veröffentlicht:2013
URI:https://archiv.ub.uni-marburg.de/diss/z2013/0411
URN: urn:nbn:de:hebis:04-z2013-04115
DOI: https://doi.org/10.17192/z2013.0411
DDC: Chemie
Titel (trans.):Ribosom-unabhängige Biosynthese von peptidischen Naturstoffen: Nichtribosomale Peptidsynthetasen und Cyclodipeptidsynthasen
Publikationsdatum:2014-02-24
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
diketopiperazines, Cyclodipeptide, cyclodipeptide synthases, Ribosom-unabhängige Peptidsynthese, nonribosomal peptide synthetases, Naturstoffchemie, Diketopiperazine, Nichtribosomale Peptide, Peptide, Antibiotikum, Molekularbiologie, Biochemie, Nonribosomal peptides, Synthetische Biologie

Summary:
Bioactive peptide natural products continue to play an important role in modern medicine since many of them represent last-resort treatments for a variety of life threatening diseases. A large fraction of those peptides are generated via ribosome-independent templated and non-templated biosynthetic pathways. Oftentimes the structural complexity of those peptides has prevented their synthesis and diversification through purely synthetic means. New approaches build on detailed knowledge about the respective biosynthetic pathways have been envisaged where fermentative in vivo or chemoenzymatic strategies are used to generate highly modified peptide natural products. To work towards this vision two templated and two non-templated biosynthetic pathways have been investigated. Both their abilities to generate particular peptide scaffolds and to subsequently decorate a given peptide backbone through the action of dedicated modification enzymes have been explored. The two templated NRPS-dependent pathways studied are the biosynthetic systems of the antitumor-antibiotic sibiromycin and the newly discovered siderophore mirubactin. The origin of the highly substituted anthranilate moiety found in sibiromycin was investigated. The pathway was shown to consist of four steps starting from the known metabolite 3-hydroxykynurenine using detailed in vitro analyses. Initially, the SAM-dependent methyltransferase SibL converts its substrate to the 4-methyl derivative, followed by hydrolysis through the PLP-dependent kynureninase SibQ leading to 3-hydroxy-4-methylanthranilic acid (3H4MAA) formation. Then the NRPS didomain SibE activates 3H4MAA and tethers it to its thiolation domain, where it then serves as the hydroxylation substrate for the FAD/NADH-dependent hydroxylase SibG, yielding the fully substituted anthranilate moiety found in sibiromycin. The siderophore mirubactin was discovered and purified from Actinosynnema mirum through cultivation under iron-limited conditions followed by activity-guided isolation. Structure elucidation was accomplished through a combination of spectroscopic, mass spectrometric and derivatization methods. Bioinformatic analyses coupled with in vitro characterization of its biosynthetic machinery, was used to identify the mirubactin gene cluster. A biosynthetic assembly route could be proposed comprising the iterative use of a stand-alone carrier-protein-bound substrate (MrbD) and the formation of an unusual O-acyl hydroxamic acid ester bond through a C-terminal condensation domain (MrbJ). In addition, two non-templated CDPS-dependent pathways responsible for nocazine biosynthesis and the generation of singly and doubly methylated ditryptophan diketopiperazines (DKPs) have been investigated. The first nocazine gene cluster could be identified through bioinformatic analyses and the biosynthetic pathway leading to the two nocazine family members nocazine E and XR334 could be elucidated through in vivo and in vitro studies. DKP-formation is carried out by a CDPS (Ndas_1148) that shows an unknown product profile forming cyclo(L-Phe-L-Tyr) and cyclo(L-Phe-L-Phe) as its main products. Tailoring of the DKP-scaffold is achieved through the combined and combinatorial action of a cyclic dipeptide oxidase (Ndas_1146/1147) and two distinct SAM-dependent O-/N-methyltransferases (Ndas_1145 and Ndas_1149). A CDPS gene cluster responsible for the formation of methylated ditryptophan DKPs was identified in A. mirum through bioinformatic genome analysis. The assembly pathway was investigated through in vivo and in vitro studies. Initially, the highly specific CDPS Amir_4627 catalyzes the formation of a formerly unknown CDPS product, namely cyclo(L-Trp-L-Trp) followed by the methylation of one or both DKP-ring nitrogens through the action of the SAM-dependent N-methyltransferase Amir_4628 generating singly and doubly methylated ditryptophan DKPs.

Bibliographie / References

  1. Tanovic, A.; Samel, S. A.; Essen, L. O.; Marahiel, M. A. Crystal structure of the termination module of a nonribosomal peptide synthetase. Science (2008), 321, 659-663.
  2. Oide, S.; Moeder, W.; Krasnoff, S.; Gibson, D.; Haas, H.; Yoshioka, K.; Turgeon, B. G. NPS6, encoding a nonribosomal peptide synthetase involved in siderophore-mediated iron metabolism, is a conserved virulence determinant of plant pathogenic ascomycetes. Plant Cell. (2006), 18, 2836-2853.
  3. Ogle, J. M.; Brodersen, D. E.; Clemons, W. M., Jr.; Tarry, M. J.; Carter, A. P.; Ramakrishnan, V. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science (2001), 292, 897-902.
  4. Puvvada, M. S.; Forrow, S. A.; Hartley, J. A.; Stephenson, P.; Gibson, I.; Jenkins, T. C.; Thurston, D. E. Inhibition of bacteriophage T7 RNA polymerase in vitro transcription by DNA-binding pyrrolo[2,1- c][1,4]benzodiazepines. Biochemistry (1997), 36, 2478-2484.
  5. Gregson, S. J.; Howard, P. W.; Hartley, J. A.; Brooks, N. A.; Adams, L. J.; Jenkins, T. C.; Kelland, L. R.; Thurston, D. E. Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity. J. Med. Chem. (2001), 44, 737-748.
  6. Fonvielle, M.; Chemama, M.; Lecerf, M.; Villet, R.; Busca, P.; Bouhss, A.; Etheve-Quelquejeu, M.; Arthur, M. Decoding the logic of the tRNA regiospecificity of nonribosomal FemX(Wv) aminoacyl transferase. Angew. Chem. Int. Ed. Engl. (2010), 49, 5115-5119.
  7. Maiya, S.; Grundmann, A.; Li, S. M.; Turner, G. The fumitremorgin gene cluster of Aspergillus fumigatus: identification of a gene encoding brevianamide F synthetase. ChemBioChem (2006), 7, 1062-1069.
  8. Stein, D. B.; Linne, U.; Hahn, M.; Marahiel, M. A. Impact of epimerization domains on the intermodular transfer of enzyme-bound intermediates in nonribosomal peptide synthesis. ChemBioChem (2006), 7, 1807-1814.
  9. Jia, J. M.; Ma, X. C.; Wu, C. F.; Wu, L. J.; Hu, G. S. Cordycedipeptide A, a new cyclodipeptide from the culture liquid of Cordyceps sinensis (Berk.) Sacc. Chem. Pharm. Bull. (Tokyo) (2005), 53, 582-583.
  10. Kopp, F.; Marahiel, M. A. Macrocyclization strategies in polyketide and nonribosomal peptide biosynthesis. Nat. Prod. Rep. (2007), 24, 735-749.
  11. Korman, S.; Tendler, M. D. Clinical investigation of cancer chemotherapeutic agents for neoplastic disease. J. New Drugs (1965), 5, 275-285.
  12. Kohn, K. W.; Bono, V. H., Jr.; Kann, H. E., Jr. Anthramycin, a new type of DNA-inhibiting antibiotic: reaction with DNA and effect on nucleic acid synthesis in mouse leukemia cells. Biochim. Biophys. Acta (1968), 155, 121-129.
  13. Correia, T.; Grammel, N.; Ortel, I.; Keller, U.; Tudzynski, P. Molecular cloning and analysis of the ergopeptine assembly system in the ergot fungus Claviceps purpurea. Chem. Biol. (2003), 10, 1281-1292.
  14. Hu, Y.; Phelan, V.; Ntai, I.; Farnet, C. M.; Zazopoulos, E.; Bachmann, B. O. Benzodiazepine biosynthesis in Streptomyces refuineus. Chem. Biol. (2007), 14, 691-701.
  15. Juguet, M.; Lautru, S.; Francou, F. X.; Nezbedova, S.; Leblond, P.; Gondry, M.; Pernodet, J. L. An iterative nonribosomal peptide synthetase assembles the pyrrole-amide antibiotic congocidine in Streptomyces ambofaciens. Chem. Biol.(2009), 16, 421-431. 77. von Dohren, H.; Keller, U.; Vater, J.; Zocher, R. Multifunctional Peptide Synthetases. Chem. Rev. (1997), 97, 2675-2706.
  16. Garcia-Estrada, C.; Ullan, R. V.; Albillos, S. M.; Fernandez-Bodega, M. A.; Durek, P.; von Dohren, H.; Martin, J. F. A single cluster of coregulated genes encodes the biosynthesis of the mycotoxins roquefortine C and meleagrin in Penicillium chrysogenum. Chem. Biol. (2011), 18, 1499- 1512.
  17. Goldsmith, M.; Tawfik, D. S. Directed enzyme evolution: beyond the low- hanging fruit. Curr. Opin. Struct. Biol. (2012), 22, 406-412.
  18. Crumbliss, A. L.; Harrington, J. M. Iron sequestration by small molecules: thermodynamic and kinetic studies of natural siderophores and synthetic model compounds, 2009; Vol. 61.
  19. Hurley, L. H. Elucidation and formulation of novel biosynthetic pathways leading to the pyrrolo[1,4]benzodiazepine antibiotics anthramycin, tomaymycin, and sibiromycin. Acc. Chem. Res. (1980), 13, 263-269.
  20. Kizu, R.; Draves, P. H.; Hurley, L. H. Correlation of DNA sequence specificity of anthramycin and tomaymycin with reaction kinetics and bending of DNA. Biochemistry (1993), 32, 8712-8722.
  21. Hertzberg, R. P.; Hecht, S. M.; Reynolds, V. L.; Molineux, I. J.; Hurley, L. H. DNA sequence specificity of the pyrrolo[1,4]benzodiazepine antitumor antibiotics. Methidiumpropyl-EDTA-iron(II) footprinting analysis of DNA binding sites for anthramycin and related drugs. Biochemistry (1986), 25, 1249-1258.
  22. Boyd, F. L.; Stewart, D.; Remers, W. A.; Barkley, M. D.; Hurley, L. H. Characterization of a unique tomaymycin-d(CICGAATTCICG)2 adduct containing two drug molecules per duplex by NMR, fluorescence, and molecular modeling studies. Biochemistry (1990), 29, 2387-2403.
  23. Petrusek, R. L.; Anderson, G. L.; Garner, T. F.; Fannin, Q. L.; Kaplan, D. J.; Zimmer, S. G.; Hurley, L. H. Pyrrol[1,4]benzodiazepine antibiotics. Proposed structures and characteristics of the in vitro deoxyribonucleic acid adducts of anthramycin, tomaymycin, sibiromycin, and neothramycins A and B. Biochemistry (1981), 20, 1111-1119.
  24. Gehring, A. M.; Mori, I. I.; Perry, R. D.; Walsh, C. T. The nonribosomal peptide synthetase HMWP2 forms a thiazoline ring during biogenesis of yersiniabactin, an iron-chelating virulence factor of yersinia pestis. Biochemistry (1998), 37, 17104.
  25. Barbeau, K.; Zhang, G.; Live, D. H.; Butler, A. Petrobactin, a photoreactive siderophore produced by the oil-degrading marine bacterium Marinobacter hydrocarbonoclasticus. J. Am. Chem. Soc. (2002), 124, 378- 379.
  26. Hurley, L. H.; Petrusek, R. Proposed structure of the anthramycin-DNA adduct. Nature (1979), 282, 529-531.
  27. Pohlmann, V.; Marahiel, M. A. Delta-amino group hydroxylation of L- ornithine during coelichelin biosynthesis. Org. Biomol. Chem. (2008), 6, 1843-1848.
  28. Magyar, A.; Zhang, X.; Kohn, H.; Widger, W. R. The antibiotic bicyclomycin affects the secondary RNA binding site of Escherichia coli transcription termination factor Rho. J. Biol. Chem. (1996), 271, 25369- 25374.
  29. Schmoock, G.; Pfennig, F.; Jewiarz, J.; Schlumbohm, W.; Laubinger, W.; Schauwecker, F.; Keller, U. Functional cross-talk between fatty acid synthesis and nonribosomal peptide synthesis in quinoxaline antibiotic- producing streptomycetes. J. Biol. Chem. (2005), 280, 4339-4349.
  30. Garg, R. P.; Gonzalez, J. M.; Parry, R. J. Biochemical characterization of VlmL, a Seryl-tRNA synthetase encoded by the valanimycin biosynthetic gene cluster. J. Biol. Chem. (2006), 281, 26785-26791.
  31. Papadopoulos, J. S.; Agarwala, R. COBALT: constraint-based alignment tool for multiple protein sequences. Bioinformatics (2007), 23, 1073-1079.
  32. Shen, N.; Guo, L.; Yang, B.; Jin, Y.; Ding, J. Structure of human tryptophanyl-tRNA synthetase in complex with tRNATrp reveals the molecular basis of tRNA recognition and specificity. Nucleic Acids Res. (2006), 34, 3246-3258.
  33. Roback, P.; Beard, J.; Baumann, D.; Gille, C.; Henry, K.; Krohn, S.; Wiste, H.; Voskuil, M. I.; Rainville, C.; Rutherford, R. A predicted operon map for Mycobacterium tuberculosis. Nucleic Acids Res. (2007), 35, 5085-5095.
  34. Caboche, S.; Pupin, M.; Leclere, V.; Fontaine, A.; Jacques, P.; Kucherov, G. NORINE: a database of nonribosomal peptides. Nucleic Acids Res. (2008), 36, D326-331.
  35. Zhou, M.; Dong, X.; Shen, N.; Zhong, C.; Ding, J. Crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase: new insights into the mechanism of tryptophan activation and implications for anti- fungal drug design. Nucleic Acids Res. (2010), 38, 3399-3413.
  36. Goujon, M.; McWilliam, H.; Li, W.; Valentin, F.; Squizzato, S.; Paern, J.; Lopez, R. A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Res. (2010), 38, W695-699.
  37. Robbel, L.; Knappe, T. A.; Linne, U.; Xie, X.; Marahiel, M. A. Erythrochelin--a hydroxamate-type siderophore predicted from the genome of Saccharopolyspora erythraea. FEBS J. (2010), 277, 663-676.
  38. Kohn, H.; Widger, W. The molecular basis for the mode of action of bicyclomycin. Curr. Drug Targets Infect. Disord. (2005), 5, 273-295.
  39. Mostad, A.; Romming, C.; Storm, B. Structure of the DNA complexing agent anthramycin. Acta Chem. Scand. B (1978), 32, 639-645.
  40. Tozuka, Z.; Takaya, T. Studies on tomaymycin. I. The structure determination of tomaymycin on the basis of NMR spectra. J. Antibiot. (Tokyo) (1983), 36, 142-146.
  41. Dai, J.; Carte, B. K.; Sidebottom, P. J.; Sek Yew, A. L.; Ng, S.; Huang, Y.; Butler, M. S. Circumdatin G, a new alkaloid from the fungus Aspergillus ochraceus. J. Nat. Prod. (2001), 64, 125-126.
  42. Seguin, J.; Moutiez, M.; Li, Y.; Belin, P.; Lecoq, A.; Fonvielle, M.; Charbonnier, J. B.; Pernodet, J. L.; Gondry, M. Nonribosomal peptide synthesis in animals: the cyclodipeptide synthase of Nematostella. Chem. Biol. (2011), 18, 1362-1368.
  43. Gross, H.; Stockwell, V. O.; Henkels, M. D.; Nowak-Thompson, B.; Loper, J. E.; Gerwick, W. H. The genomisotopic approach: a systematic method to isolate products of orphan biosynthetic gene clusters. Chem. Biol. (2007), 14, 53-63.
  44. Kodani, S.; Bicz, J.; Song, L.; Deeth, R. J.; Ohnishi-Kameyama, M.; Yoshida, M.; Ochi, K.; Challis, G. L. Structure and biosynthesis of scabichelin, a novel tris-hydroxamate siderophore produced by the plant pathogen Streptomyces scabies 87.22. Org. Biomol. Chem. (2013).
  45. Burger, A. M.; Loadman, P. M.; Thurston, D. E.; Schultz, R.; Fiebig, H. H.; Bibby, M. C. Preclinical pharmacology of the pyrrolobenzodiazepine (PBD) monomer DRH-417 (NSC 709119). J.Chemother. (2007), 19, 66-78.
  46. Beringer, M.; Rodnina, M. V. The ribosomal peptidyl transferase. Mol. Cell. (2007), 26, 311-321.
  47. G. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. (2011), 7, 539.
  48. Pierre, J. L.; Fontecave, M.; Crichton, R. R. Chemistry for an essential biological process: the reduction of ferric iron. Biometals (2002), 15, 341- 346.
  49. Arora, S. K. Structure of tomaymycin, a DNA binding antitumor antibiotic. J. Antibiot. (Tokyo) (1981), 34, 462-464.
  50. Baltz, R. H. Function of MbtH homologs in nonribosomal peptide biosynthesis and applications in secondary metabolite discovery. J. Ind. Microbiol. Biotechnol. (2011), 38, 1747-1760.
  51. Chirala, S. S.; Wakil, S. J. Structure and function of animal fatty acid synthase. Lipids (2004), 39, 1045-1053.
  52. Baraldi, P. G.; Cacciari, B.; Guiotto, A.; Romagnoli, R.; Spalluto, G.; Leoni, A.; Bianchi, N.; Feriotto, G.; Rutigliano, C.; Mischiati, C.; Gambari, R. [2,1-c][1,4]benzodiazepine (PBD)-distamycin hybrid inhibits DNA binding to transcription factor Sp1. Nucleos. Nucleot. Nucl. (2000), 19, 1219-1229.
  53. Yin, W. B.; Grundmann, A.; Cheng, J.; Li, S. M. Acetylaszonalenin biosynthesis in Neosartorya fischeri. Identification of the biosynthetic gene cluster by genomic mining and functional proof of the genes by biochemical investigation. J. Biol. Chem. (2009), 284, 100-109.
  54. Liu, C. C.; Schultz, P. G. Adding new chemistries to the genetic code. Annu. Rev. Biochem. (2010), 79, 413-444.
  55. Kotecha, M.; Kluza, J.; Wells, G.; O'Hare, C. C.; Forni, C.; Mantovani, R.; Howard, P. W.; Morris, P.; Thurston, D. E.; Hartley, J. A.; Hochhauser, D. Inhibition of DNA binding of the NF-Y transcription factor by the pyrrolobenzodiazepine-polyamide conjugate GWL-78. Mol. Cancer Ther. (2008), 7, 1319-1328.
  56. Lambalot, R. H.; Gehring, A. M.; Flugel, R. S.; Zuber, P.; LaCelle, M.; Marahiel, M. A.; Reid, R.; Khosla, C.; Walsh, C. T. A new enzyme superfamily -the phosphopantetheinyl transferases. Chem. Biol. (1996), 3, 923-936.
  57. Chen, Z.; Gregson, S. J.; Howard, P. W.; Thurston, D. E. A novel approach to the synthesis of cytotoxic C2-C3 unsaturated pyrrolo[2,1- c]benzodiazepines (PBDs) with conjugated acrylyl C2-substituents. Bioorg. Med. Chem. Lett.(2004), 14, 1547-1549. References 183
  58. Kanoh, K.; Kohno, S.; Katada, J.; Hayashi, Y.; Muramatsu, M.; Uno, I. Antitumor activity of phenylahistin in vitro and in vivo. Biosci. Biotechnol. Biochem. (1999), 63, 1130-1133.
  59. Yanagisawa, T.; Sumida, T.; Ishii, R.; Takemoto, C.; Yokoyama, S. A paralog of lysyl-tRNA synthetase aminoacylates a conserved lysine residue in translation elongation factor P. Nat. Struct. Mol. Biol. (2010), 17, 1136- 1143.
  60. Tiberghien, A. C.; Hagan, D.; Howard, P. W.; Thurston, D. E. Application of the Stille coupling reaction to the synthesis of C2-substituted endo-exo unsaturated pyrrolo[2,1-c][1,4]benzodiazepines (PBDs). Bioorg. Med. Chem. Lett (2004), 14, 5041-5044.
  61. Li, S. M. Applications of dimethylallyltryptophan synthases and other indole prenyltransferases for structural modification of natural products.
  62. Puvvada, M. S.; Hartley, J. A.; Jenkins, T. C.; Thurston, D. E. A quantitative assay to measure the relative DNA-binding affinity of pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) antitumour antibiotics based on the inhibition of restriction endonuclease BamHI. Nucleic Acids Res. (1993), 21, 3671-3675.
  63. Sareen, D.; Steffek, M.; Newton, G. L.; Fahey, R. C. ATP-dependent L- cysteine:1D-myo-inosityl 2-amino-2-deoxy-alpha-D-glucopyranoside ligase, mycothiol biosynthesis enzyme MshC, is related to class I cysteinyl-tRNA synthetases. Biochemistry (2002), 41, 6885-6890.
  64. Dertz, E. A.; Xu, J.; Stintzi, A.; Raymond, K. N. Bacillibactin-mediated iron transport in Bacillus subtilis. J. Am. Chem. Soc. (2006), 128, 22-23.
  65. Ross, W. Benzodiazepine alkaloids; Academic Press: San Diego, 1990.
  66. benzodiazepine conjugates: synthesis and biological evaluation. Mini Rev. Med. Chem. (2003), 3, 323-339.
  67. Meneely, K. M.; Lamb, A. L. Biochemical characterization of a flavin adenine dinucleotide-dependent monooxygenase, ornithine hydroxylase from Pseudomonas aeruginosa, suggests a novel reaction mechanism. Biochemistry (2007), 46, 11930-11937.
  68. Stachelhaus, T.; Huser, A.; Marahiel, M. A. Biochemical characterization of peptidyl carrier protein (PCP), the thiolation domain of multifunctional peptide synthetases. Chem. Biol. (1996), 3, 913-921.
  69. Gardiner, D. M.; Howlett, B. J. Bioinformatic and expression analysis of the putative gliotoxin biosynthetic gene cluster of Aspergillus fumigatus. FEMS Microbiol. Lett. (2005), 248, 241-248.
  70. Pyrrolo[1,4]benzodiazepine antibiotics. Biosynthesis of the antitumor antibiotic sibiromycin by Streptosporangium sibiricum. Biochemistry (1979), 18, 4225-4229.
  71. Kanzaki, H.; Yanagisawa, S.; Nitoda, T. Biosynthetic intermediates of the tetradehydro cyclic dipeptide albonoursin produced by Streptomyces albulus KO-23. J. Antibiot. (Tokyo) (2000), 53, 1257-1264.
  72. Tseng, C. C.; Bruner, S. D.; Kohli, R. M.; Marahiel, M. A.; Walsh, C. T.; Sieber, S. A. Characterization of the surfactin synthetase C-terminal thioesterase domain as a cyclic depsipeptide synthase. Biochemistry (2002), 41, 13350-13359.
  73. Horwitz, S. B.; Chang, S. C.; Grollman, A. P.; Borkovec, A. B. Chemosterilant action of anthramycin: a proposed mechanism. Science (1971), 174, 159-161.
  74. Konishi, M.; Ohkuma, H.; Naruse, N.; Kawaguchi, H. Chicamycin, a new antitumor antibiotic. II. Structure determination of chicamycins A and B.
  75. Li, W.; Chou, S.; Khullar, A.; Gerratana, B. Cloning and characterization of the biosynthetic gene cluster for tomaymycin, an SJG-136 monomeric analog. Appl. Environ. Microbiol. (2009), 75, 2958-2963.
  76. Rao, S. T.; Rossmann, M. G. Comparison of super-secondary structures in proteins. J. Mol. Biol. (1973), 76, 241-256.
  77. Kopka, M. L.; Goodsell, D. S.; Baikalov, I.; Grzeskowiak, K.; Cascio, D.; Dickerson, R. E. Crystal structure of a covalent DNA-drug adduct: anthramycin bound to C-C-A-A-C-G-T-T-G-G and a molecular explanation of specificity. Biochemistry (1994), 33, 13593-13610.
  78. Conti, E.; Franks, N. P.; Brick, P. Crystal structure of firefly luciferase throws light on a superfamily of adenylate-forming enzymes. Structure (1996), 4, 287-298.
  79. Borthwick, A. D. 2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products. Chem. Rev. (2012), 112, 3641- 3716.
  80. Tabata, I.; Hayakawa, K.; Shinozuka, T.; Tazima, T.; Matsunaga, F. [Diagnosis of postbiliary surgery syndrome by endoscopic retrograde cholangio-pancreatography (author's transl)]. Rinsho Hoshasen (1977), 22, 1091-1099.
  81. Kanzaki, H.; Imura, D.; Sashida, R.; Kobayashi, A.; Kawazu, K. Effective production of dehydro cyclic dipeptide albonoursin exhibiting pronuclear fusion inhibitory activity. I. Taxonomy and fermentation. J. Antibiot. (Tokyo) (1999), 52, 1017-1022.
  82. Thurston, D. E.; Bose, D. S.; Howard, P. W.; Jenkins, T. C.; Leoni, A.; Baraldi, P. G.; Guiotto, A.; Cacciari, B.; Kelland, L. R.; Foloppe, M. P.; Rault, S. Effect of A-ring modifications on the DNA-binding behavior and cytotoxicity of pyrrolo[2,1-c][1,4]benzodiazepines. J. Med. Chem. (1999), 42, 1951-1964.
  83. Gregson, S. J.; Howard, P. W.; Barcella, S.; Nakamya, A.; Jenkins, T. C.; Kelland, L. R.; Thurston, D. E. Effect of C2/C3-endo unsaturation on the cytotoxicity and DNA-binding reactivity of pyrrolo[2,1- c][1,4]benzodiazepines. Bioorg. Med. Chem. Lett. (2000), 10, 1849-1851.
  84. Gregson, S. J.; Howard, P. W.; Corcoran, K. E.; Barcella, S.; Yasin, M. M.; Hurst, A. A.; Jenkins, T. C.; Kelland, L. R.; Thurston, D. E. Effect of C2- exo unsaturation on the cytotoxicity and DNA-binding reactivity of pyrrolo[2,1-c][1,4]benzodiazepines. Bioorg. Med. Chem. Lett. (2000), 10, 1845-1847.
  85. Cargill, C.; Bachmann, E.; Zbinden, G. Effects of daunomycin and anthramycin on electrocardiogram and mitochondrial metabolism of the rat heart. J. Natl. Cancer Inst. (1974), 53, 481-486.
  86. Kanzaki, H.; Yanagisawa, S.; Nitoda, T. Enzymatic synthesis of dehydro cyclo(His-Phe)s, References 186
  87. Li, S. M. Evolution of aromatic prenyltransferases in the biosynthesis of indole derivatives. Phytochemistry (2009), 70, 1746-1757.
  88. Martin, R. B. Free energies and equilibria of peptide bond hydrolysis and formation. Biopolymers (1998), 45, 351-353.
  89. Konz, D.; Marahiel, M. A. How do peptide synthetases generate structural diversity? Chem. Biol. (1999), 6, R39-48.
  90. Moon, Y. H.; Tanabe, T.; Funahashi, T.; Shiuchi, K.; Nakao, H.; Yamamoto, S. Identification and characterization of two contiguous operons required for aerobactin transport and biosynthesis in Vibrio mimicus. Microbiol. Immunol. (2004), 48, 389-398.
  91. Hu, W. P.; Tsai, F. Y.; Yu, H. S.; Sung, P. J.; Chang, L. S.; Wang, J. J. Induction of apoptosis by DC-81-indole conjugate agent through NF- kappaB and JNK/AP-1 pathway. Chem. Res. Toxicol. (2008), 21, 1330- 1336.
  92. Keating, T. A.; Walsh, C. T. Initiation, elongation, and termination strategies in polyketide and polypeptide antibiotic biosynthesis. Curr. Opin. Chem. Biol. (1999), 3, 598-606.
  93. Heguy, A.; Cai, P.; Meyn, P.; Houck, D.; Russo, S.; Michitsch, R.; Pearce, C.; Katz, B.; Bringmann, G.; Feineis, D.; Taylor, D. L.; Tyms, A. S. Isolation and characterization of the fungal metabolite 3-O- methylviridicatin as an inhibitor of tumour necrosis factor alpha-induced human immunodeficiency virus replication. Antivir. Chem. Chemother. (1998), 9, 149-155.
  94. Nishioka, Y.; Beppu, T.; Kosaka, M.; Arima, K. Mode of action of tomaymycin. J.Antibiot. (Tokyo) (1972), 25, 660-667.
  95. Schwarzer, D.; Marahiel, M. A. Multimodular biocatalysts for natural product assembly. Die Naturwissenschaften (2001), 88, 93-101.
  96. Goffin, C.; Ghuysen, J. M. Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol. Mol. Biol. Rev. (1998), 62, 1079-1093. 58. Fischbach, M. A.; Walsh, C. T.; Clardy, J. The evolution of gene collectives: How natural selection drives chemical innovation. Proc. Natl.
  97. Yonemoto, I. T.; Li, W.; Khullar, A.; Reixach, N.; Gerratana, B. Mutasynthesis of a potent anticancer sibiromycin analogue. ACS Chem. Biol.(2012), 7, 973-977.
  98. Takeuchi, T.; Miyamoto, T.; Ishizuka, M.; Naganawa, H.; Kondo, S. Neothramycins A and B, new antitumor antibiotics. J. Antibiot. (Tokyo) (1976), 29, 93-96.
  99. Rottig, M.; Medema, M. H.; Blin, K.; Weber, T.; Rausch, C.; Kohlbacher, O. NRPSpredictor2--a web server for predicting NRPS adenylation domain specificity. Nucleic Acids Res.(2011), 39, W362-367.
  100. Eriani, G.; Delarue, M.; Poch, O.; Gangloff, J.; Moras, D. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature (1990), 347, 203-206.
  101. Jencks, W. P. Handbook of Biochemistry and Molceular Biology, Physical and Chemical Data; 3rd ed.; CRC Press, 1976; Vol. I. 62. Belin, P.; Moutiez, M.; Lautru, S.; Seguin, J.; Pernodet, J. L.; Gondry, M. The nonribosomal synthesis of diketopiperazines in tRNA-dependent cyclodipeptide synthase pathways. Nat. Prod. Rep. (2012), 29, 961-979.
  102. Degrassi, G.; Aguilar, C.; Bosco, M.; Zahariev, S.; Pongor, S.; Venturi, V. Plant growth-promoting Pseudomonas putida WCS358 produces and secretes four cyclic dipeptides: cross-talk with quorum sensing bacterial sensors. Curr. Microbiol. (2002), 45, 250-254.
  103. Gauze, G. F.; Preobrazhenskaia, T. P.; Ivanitskaia, L. P.; Sveshnikova, M. A. [Production of the antibiotic sibiromycin by the Streptosporangium sibiricum sp. nov. culture]. Antibiotiki (1969), 14, 963-969. References 181
  104. Holden, M. T.; Ram Chhabra, S.; de Nys, R.; Stead, P.; Bainton, N. J.; Hill, P. J.; Manefield, M.; Kumar, N.; Labatte, M.; England, D.; Rice, S.; Givskov, M.; Salmond, G. P.; Stewart, G. S.; Bycroft, B. W.; Kjelleberg, S.; Williams, P. Quorum-sensing cross talk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other gram-negative bacteria. Mol. Microbiol. (1999), 33, 1254-1266.
  105. Radzicka, A.; Wolfenden, R. Rates of Uncatalyzed Peptide Bond Hydrolysis in Neutral Solution and the Transition State Affinities of Proteases. J. Am. Chem. Soc. (1996), 118, 6105-6109.
  106. Kohn, K. W.; Spears, C. L. Reaction of anthramycin with deoxyribonucleic acid. J. Mol. Biol. (1970), 51, 551-572.
  107. Petrusek, R. L.; Uhlenhopp, E. L.; Duteau, N.; Hurley, L. H. Reaction of anthramycin with DNA. Biological consequences of DNA damage in normal and xeroderma pigmentosum cell. J. Biol. Chem. (1982), 257, 6207-6216.
  108. Kumar, R.; Lown, J. W. Recent developments in novel pyrrolo[2,1-
  109. Gehring, A. M.; Mori, I.; Walsh, C. T. Reconstitution and characterization of the Escherichia coli enterobactin synthetase from EntB, EntE, and EntF. Biochemistry (1998), 37, 2648-2659.
  110. Ellison, D. W.; Miller, V. L. Regulation of virulence by members of the MarR/SlyA family. Curr. Opin. Microbiol. (2006), 9, 153-159.
  111. Johnson, J. A.; Lu, Y. Y.; Van Deventer, J. A.; Tirrell, D. A. Residue- specific incorporation of non-canonical amino acids into proteins: recent developments and applications. Curr. Opin. Chem. Biol. (2010), 14, 774- 780.
  112. Itoh, J.; Watabe, H.; Ishii, S.; Gomi, S.; Nagasawa, M.; Yamamoto, H.; Shomura, T.; Sezaki, M.; Kondo, S. Sibanomicin, a new pyrrolo[1,4]benzodiazepine antitumor antibiotic produced by a Micromonospora sp. J. Antibiot. (Tokyo) (1988), 41, 1281-1284.
  113. Cryle, M. J.; Bell, S. G.; Schlichting, I. Structural and biochemical characterization of the cytochrome P450 CypX (CYP134A1) from Bacillus subtilis: a cyclo-L-leucyl-L-leucyl dipeptide oxidase. Biochemistry (2010), 49, 7282-7296.
  114. Kobayashi, T.; Nureki, O.; Ishitani, R.; Yaremchuk, A.; Tukalo, M.; Cusack, S.; Sakamoto, K.; Yokoyama, S. Structural basis for orthogonal tRNA specificities of tyrosyl-tRNA synthetases for genetic code expansion. Nat. Struct. Biol. (2003), 10, 425-432.
  115. Miyamoto, M.; Kondo, S.; Naganawa, H.; Maeda, K.; Ohno, M. Structure and synthesis of neothramycin. J. Antibiot. (Tokyo) (1977), 30, 340-343.
  116. Arima, K.; Kosaka, M.; Tamura, G.; Imanaka, H.; Sakai, H. Studies on tomaymycin, a new antibiotic. I. Isolation and properties of tomaymycin.
  117. Karp, G. M.; Manfredi, M. C.; Guaciaro, M. A.; Ortlip, C. L.; Marc, P.; Szamosi, I. T. Synthesis and herbicidal activity of 1H-1,4-benzodiazepine- 2,5-diones. J. Agric. Food. Chem. (1997), 45, 493-500. c][1,4]benzodiazepine-5,11(10H)-dione as anxiolytic agents. J. Med. Chem. (1978), 21, 1087-1089.
  118. Walsh, C. T.; Chen, H.; Keating, T. A.; Hubbard, B. K.; Losey, H. C.; Luo, L.; Marshall, C. G.; Miller, D. A.; Patel, H. M. Tailoring enzymes that modify nonribosomal peptides during and after chain elongation on NRPS assembly lines. Curr. Opin. Chem. Biol. (2001), 5, 525-534. References 175
  119. Konz, D.; Klens, A.; Schorgendorfer, K.; Marahiel, M. A. The bacitracin biosynthesis operon of Bacillus licheniformis ATCC 10716: molecular characterization of three multi-modular peptide synthetases. Chem. Biol. (1997), 4, 927-937. References 179
  120. May, J. J.; Wendrich, T. M.; Marahiel, M. A. The dhb operon of Bacillus subtilis encodes the biosynthetic template for the catecholic siderophore 2,3-dihydroxybenzoate-glycine-threonine trimeric ester bacillibactin. J. Biol. Chem. (2001), 276, 7209-7217.
  121. Kessler, N.; Schuhmann, H.; Morneweg, S.; Linne, U.; Marahiel, M. A. The linear pentadecapeptide gramicidin is assembled by four multimodular nonribosomal peptide synthetases that comprise 16 modules with 56 catalytic domains. J. Biol. Chem. (2004), 279, 7413-7419.
  122. Alekshun, M. N.; Levy, S. B. The mar regulon: multiple resistance to antibiotics and other toxic chemicals. Trends Microbiol. (1999), 7, 410- 413.
  123. Pepper, C. J.; Hambly, R. M.; Fegan, C. D.; Delavault, P.; Thurston, D. E. The novel sequence-specific DNA cross-linking agent SJG-136 (NSC 694501) has potent and selective in vitro cytotoxicity in human B-cell chronic lymphocytic leukemia cells with evidence of a p53-independent mechanism of cell kill. Cancer Res. (2004), 64, 6750-6755.
  124. Graves, D. E.; Pattaroni, C.; Krishnan, B. S.; Ostrander, J. M.; Hurley, L. H.; Krugh, T. R. The reaction of anthramycin with DNA. Proton and carbon nuclear magnetic resonance studies on the structure of the anthramycin-DNA adduct. J. Biol. Chem. (1984), 259, 8202-8209.
  125. Leimgruber, W.; Batcho, A. D.; Schenker, F. The structure of anthramycin. J. Am. Chem. Soc. (1965), 87, 5793-5795.
  126. Bode, H. B.; Wenzel, S. C.; Irschik, H.; Hofle, G.; Muller, R. Unusual biosynthesis of leupyrrins in the myxobacterium Sorangium cellulosum.
  127. Tang, M. R.; Sternberg, D.; Behr, R. K.; Sloma, A.; Berka, R. M. Use of transcriptional profiling and bioinformatics to solve production problems. Eliminating red pigment production in a Bacillus subtilis train producing hyaluornic acid. Ind. Biotechnol. (2006), 2, 66-74.
  128. Stein, T.; Kluge, B.; Vater, J.; Franke, P.; Otto, A.; Wittmann-Liebold, B. Gramicidin S synthetase 1 (phenylalanine racemase), a prototype of amino acid racemases containing the cofactor 4'-phosphopantetheine. Biochemistry (1995), 34, 4633-4642.
  129. Marahiel, M. A. Working outside the protein-synthesis rules: insights into non-ribosomal peptide synthesis. J. Pept. Sci. (2009), 15, 799-807.
  130. Lubawy, W. C.; Dallam, R. A.; Hurley, L. H. Protection against anthramycin-induced toxicity in mice by coenzyme Q10. J. Natl. Cancer Inst. (1980), 64, 105-109.
  131. McAlpine, J. B.; Banskota, A. H.; Charan, R. D.; Schlingmann, G.; Zazopoulos, E.; Piraee, M.; Janso, J.; Bernan, V. S.; Aouidate, M.; Farnet, C. M.; Feng, X.; Zhao, Z.; Carter, G. T. Biosynthesis of diazepinomicin/ECO-4601, a Micromonospora secondary metabolite with a novel ring system. J. Nat. Prod. (2008), 71, 1585-1590.
  132. Healy, F. G.; Wach, M.; Krasnoff, S. B.; Gibson, D. M.; Loria, R. The txtAB genes of the plant pathogen Streptomyces acidiscabies encode a peptide synthetase required for phytotoxin thaxtomin A production and pathogenicity. Mol.Microbiol. (2000), 38, 794-804. References 189
  133. Gondry, M.; Lautru, S.; Fusai, G.; Meunier, G.; Menez, A.; Genet, R. Cyclic dipeptide oxidase from Streptomyces noursei. Isolation, purification and partial characterization of a novel, amino acyl alpha,beta- dehydrogenase. Eur. J. Biochem. (2001), 268, 1712-1721.
  134. Zhang, Y.; Wang, L.; Schultz, P. G.; Wilson, I. A. Crystal structures of apo wild-type M. jannaschii tyrosyl-tRNA synthetase (TyrRS) and an engineered TyrRS specific for O-methyl-L-tyrosine. Protein Sci. (2005), 14, 1340-1349.
  135. Gardiner, D. M.; Cozijnsen, A. J.; Wilson, L. M.; Pedras, M. S.; Howlett, B. J. The sirodesmin biosynthetic gene cluster of the plant pathogenic fungus Leptosphaeria maculans. Mol. Microbiol. (2004), 53, 1307-1318.
  136. Zocher, R.; Nihira, T.; Paul, E.; Madry, N.; Peeters, H.; Kleinkauf, H.; Keller, U. Biosynthesis of cyclosporin A: partial purification and properties of a multifunctional enzyme from Tolypocladium inflatum. Biochemistry (1986), 25, 550-553.
  137. Schneider, T. L.; Shen, B.; Walsh, C. T. Oxidase domains in epothilone and bleomycin biosynthesis: thiazoline to thiazole oxidation during chain elongation. Biochemistry (2003), 42, 9722-9730.
  138. Antonow, D.; Cooper, N.; Howard, P. W.; Thurston, D. E. Parallel synthesis of a novel C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine (PBD) library. J. Comb. Chem. (2007), 9, 437-445.
  139. Hurley, L. H.; Zmijewski, M.; Chang, C. J. Biosynthesis of anthramycin. Determination of the labeling pattern by the use of radioactive and stable isotope techniques. J. Am. Chem. Soc. (1975), 97, 4372-4378.
  140. Schultz, A. W.; Oh, D. C.; Carney, J. R.; Williamson, R. T.; Udwary, D. W.; Jensen, P. R.; Gould, S. J.; Fenical, W.; Moore, B. S. Biosynthesis and structures of cyclomarins and cyclomarazines, prenylated cyclic peptides of marine actinobacterial origin. J. Am. Chem. Soc. (2008), 130, 4507- 4516.
  141. Samel, S. A.; Marahiel, M. A.; Essen, L. O. How to tailor non-ribosomal peptide products--new clues about the structures and mechanisms of modifying enzymes. Mol. Biosyst. (2008), 4, 387-393.
  142. Hur, G. H.; Vickery, C. R.; Burkart, M. D. Explorations of catalytic domains in non-ribosomal peptide synthetase enzymology. Nat. Prod. Rep. (2012), 29, 1074-1098.
  143. Lautru, S.; Deeth, R. J.; Bailey, L. M.; Challis, G. L. Discovery of a new peptide natural product by Streptomyces coelicolor genome mining. Nat. Chem. Biol. (2005), 1, 265-269.
  144. Lazos, O.; Tosin, M.; Slusarczyk, A. L.; Boakes, S.; Cortes, J.; Sidebottom, P. J.; Leadlay, P. F. Biosynthesis of the putative siderophore erythrochelin requires unprecedented crosstalk between separate nonribosomal peptide gene clusters. Chem. Biol. (2010), 17, 160-173.
  145. Kadi, N.; Oves-Costales, D.; Barona-Gomez, F.; Challis, G. L. A new family of ATP-dependent oligomerization-macrocyclization biocatalysts. Nat. Chem. Biol. (2007), 3, 652-656.
  146. Barona-Gomez, F.; Wong, U.; Giannakopulos, A. E.; Derrick, P. J.; Challis, G. L. Identification of a cluster of genes that directs desferrioxamine biosynthesis in Streptomyces coelicolor M145. J. Am. Chem. Soc. (2004), 126, 16282-16283.
  147. Gourdeau, H.; McAlpine, J. B.; Ranger, M.; Simard, B.; Berger, F.; Beaudry, F.; Farnet, C. M.; Falardeau, P. Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand. Cancer Chemother. Pharmacol. (2008), 61, 911-921.
  148. Stachelhaus, T.; Mootz, H. D.; Bergendahl, V.; Marahiel, M. A. Peptide bond formation in nonribosomal peptide biosynthesis. Catalytic role of the condensation domain. J. Biol. Chem. (1998), 273, 22773-22781.
  149. Mootz, H. D.; Finking, R.; Marahiel, M. A. 4'-phosphopantetheine transfer in primary and secondary metabolism of Bacillus subtilis. J. Biol. Chem. (2001), 276, 37289-37298.
  150. Leys, D.; Mowat, C. G.; McLean, K. J.; Richmond, A.; Chapman, S. K.; Walkinshaw, M. D.; Munro, A. W. Atomic structure of Mycobacterium tuberculosis CYP121 to 1.06 A reveals novel features of cytochrome P450.
  151. McLean, K. J.; Cheesman, M. R.; Rivers, S. L.; Richmond, A.; Leys, D.; Chapman, S. K.; Reid, G. A.; Price, N. C.; Kelly, S. M.; Clarkson, J.; Smith, W. E.; Munro, A. W. Expression, purification and spectroscopic characterization of the cytochrome P450 CYP121 from Mycobacterium tuberculosis. J. Inorg. Biochem. (2002), 91, 527-541.
  152. Seward, H. E.; Roujeinikova, A.; McLean, K. J.; Munro, A. W.; Leys, D. Crystal structure of the Mycobacterium tuberculosis P450 CYP121- fluconazole complex reveals new azole drug-P450 binding mode. J. Biol. Chem. (2006), 281, 39437-39443.
  153. Cole, S. T.; Brosch, R.; Parkhill, J.; Garnier, T.; Churcher, C.; Harris, D.; Gordon, S. V.; Eiglmeier, K.; Gas, S.; Barry, C. E., 3rd; Tekaia, F.; Badcock, K.; Basham, D.; Brown, D.; Chillingworth, T.; Connor, R.; Davies, R.; Devlin, K.; Feltwell, T.; Gentles, S.; Hamlin, N.; Holroyd, S.; Hornsby, T.; Jagels, K.; Krogh, A.; McLean, J.; Moule, S.; Murphy, L.; Oliver, K.; Osborne, J.; Quail, M. A.; Rajandream, M. A.; Rogers, J.; Rutter, S.; Seeger, K.; Skelton, J.; Squares, R.; Squares, S.; Sulston, J. E.; Taylor, K.; Whitehead, S.; Barrell, B. G. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature (1998), 393, 537-544.
  154. Bornscheuer, U. T.; Huisman, G. W.; Kazlauskas, R. J.; Lutz, S.; Moore, J. C.; Robins, K. Engineering the third wave of biocatalysis. Nature (2012), 485, 185-194.
  155. Funabashi, M.; Yang, Z.; Nonaka, K.; Hosobuchi, M.; Fujita, Y.; Shibata, T.; Chi, X.; Van Lanen, S. G. An ATP-independent strategy for amide bond formation in antibiotic biosynthesis. Nat. Chem. Biol. (2010), 6, 581-586.
  156. Keating, T. A.; Marshall, C. G.; Walsh, C. T.; Keating, A. E. The structure of VibH represents nonribosomal peptide synthetase condensation, cyclization and epimerization domains. Nat. Struct. Biol. (2002), 9, 522- 526.
  157. Gerratana, B. Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines. Med. Res. Rev.(2012), 32, 254-293.
  158. Healy, F. G.; Krasnoff, S. B.; Wach, M.; Gibson, D. M.; Loria, R. Involvement of a cytochrome P450 monooxygenase in thaxtomin A biosynthesis by Streptomyces acidiscabies. J. Bacteriol. (2002), 184, 2019- 2029.
  159. Park, D. K.; Lee, K. E.; Baek, C. H.; Kim, I. H.; Kwon, J. H.; Lee, W. K.; Lee, K. H.; Kim, B. S.; Choi, S. H.; Kim, K. S. Cyclo(Phe-Pro) modulates the expression of ompU in Vibrio spp. J. Bacteriol. (2006), 188, 2214- 2221.
  160. Magarvey, N. A.; Haltli, B.; He, M.; Greenstein, M.; Hucul, J. A. Biosynthetic pathway for mannopeptimycins, lipoglycopeptide antibiotics active against drug-resistant gram-positive pathogens. Antimicrob. Agents Chemother. (2006), 50, 2167-2177.
  161. Raymond, K. N.; Dertz, E. A.; Kim, S. S. Enterobactin: an archetype for microbial iron transport. Proc. Natl. Acad. Sci. U S A (2003), 100, 3584- 3588.
  162. Cain, C. C.; Lee, D.; Waldo, R. H., 3rd; Henry, A. T.; Casida, E. J., Jr.; Wani, M. C.; Wall, M. E.; Oberlies, N. H.; Falkinham, J. O., 3rd Synergistic antimicrobial activity of metabolites produced by a nonobligate bacterial predator. Antimicrob. Agents. Chemother. (2003), 47, 2113-2117.
  163. Suto, K.; Shimizu, Y.; Watanabe, K.; Ueda, T.; Fukai, S.; Nureki, O.; Tomita, K. Crystal structures of leucyl/phenylalanyl-tRNA-protein transferase and its complex with an aminoacyl-tRNA analog. EMBO J. (2006), 25, 5942-5950.
  164. Mootz, H. D.; Marahiel, M. A. The tyrocidine biosynthesis operon of Bacillus brevis: complete nucleotide sequence and biochemical characterization of functional internal adenylation domains. J. Bacteriol. (1997), 179, 6843-6850.
  165. de Lorenzo, V.; Bindereif, A.; Paw, B. H.; Neilands, J. B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. (1986), 165, 570-578.
  166. Miethke, M.; Marahiel, M. A. Siderophore-based iron acquisition and pathogen control. Microbiol. Mol. Biol. Rev. (2007), 71, 413-451.
  167. Carrano, C. J.; Raymond, K. N. Coordination chemistry of microbial iron transport compounds: rhodotorulic acid and iron uptake in Rhodotorula pilimanae. J. Bacteriol. (1978), 136, 69-74.
  168. Roy, H.; Ibba, M. RNA-dependent lipid remodeling by bacterial multiple peptide resistance factors. Proc. Natl. Acad. Sci. U S A (2008), 105, 4667- 4672.
  169. Amann, R. I.; Ludwig, W.; Schleifer, K. H. Phylogenetic identification and in situ detection of individual microbial cells without cultivation. Microbiol. Rev. (1995), 59, 143-169.
  170. Dimise, E. J.; Widboom, P. F.; Bruner, S. D. Structure elucidation and biosynthesis of fuscachelins, peptide siderophores from the moderate thermophile Thermobifida fusca. Proc. Natl. Acad. Sci. U S A (2008), 105, 15311-15316.
  171. Francklyn, C. S. DNA polymerases and aminoacyl-tRNA synthetases: shared mechanisms for ensuring the fidelity of gene expression. Biochemistry (2008), 47, 11695-11703.
  172. Belin, P.; Le Du, M. H.; Fielding, A.; Lequin, O.; Jacquet, M.; Charbonnier, J. B.; Lecoq, A.; Thai, R.; Courcon, M.; Masson, C.; Dugave, C.; Genet, R.; Pernodet, J. L.; Gondry, M. Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis. Proc. Natl. Acad.Sci. U S A (2009), 106, 7426-7431. References 187
  173. Li, W.; Khullar, A.; Chou, S.; Sacramo, A.; Gerratana, B. Biosynthesis of sibiromycin, a potent antitumor antibiotic. Appl. Environ. Microbiol. (2009), 75, 2869-2878.
  174. Roy, H.; Ibba, M. Broad range amino acid specificity of RNA-dependent lipid remodeling by multiple peptide resistance factors. J. Biol. Chem. (2009), 284, 29677-29683.
  175. Ulanova, D.; Novotna, J.; Smutna, Y.; Kamenik, Z.; Gazak, R.; Sulc, M.; Sedmera, P.; Kadlcik, S.; Plhackova, K.; Janata, J. Mutasynthesis of lincomycin derivatives with activity against drug-resistant staphylococci. Antimicrob. Agents Chemother. (2010), 54, 927-930.
  176. Young, T. S.; Schultz, P. G. Beyond the canonical 20 amino acids: expanding the genetic lexicon. J. Biol. Chem. (2010), 285, 11039-11044.
  177. Li, J.; Wang, W.; Xu, S. X.; Magarvey, N. A.; McCormick, J. K. Lactobacillus reuteri-produced cyclic dipeptides quench agr-mediated expression of toxic shock syndrome toxin-1 in staphylococci. Proc. Natl.
  178. Roy, H.; Zou, S. B.; Bullwinkle, T. J.; Wolfe, B. S.; Gilreath, M. S.; Forsyth, C. J.; Navarre, W. W.; Ibba, M. The tRNA synthetase paralog PoxA modifies elongation factor-P with (R)-beta-lysine. Nat. Chem. Biol. (2011), 7, 667-669.
  179. Francklyn, C. S.; Minajigi, A. tRNA as an active chemical scaffold for diverse chemical transformations. FEBS Lett. (2010), 584, 366-375.
  180. Watrous, J.; Roach, P.; Alexandrov, T.; Heath, B. S.; Yang, J. Y.; Kersten, R. D.; van der Voort, M.; Pogliano, K.; Gross, H.; Raaijmakers, J. M.; Moore, B. S.; Laskin, J.; Bandeira, N.; Dorrestein, P. C. Mass spectral molecular networking of living microbial colonies. Proc. Natl. Acad. Sci. U S A (2012), 109, E1743-1752.
  181. Hurley, L. H.; Gairola, C. Pyrrolo (1,4) benzodiazepine antitumor antibiotics: Biosynthetic studies on the conversion of tryptophan to the anthranilic acid moieties of sibiromycin and tomaymycin. Antimicrob. Agents Chemother. (1979), 15, 42-45.
  182. Watrous, J. D.; Dorrestein, P. C. Imaging mass spectrometry in microbiology. Nat. Rev. Microbiol.(2011), 9, 683-694.
  183. Chiu, H. T.; Hubbard, B. K.; Shah, A. N.; Eide, J.; Fredenburg, R. A.; Walsh, C. T.; Khosla, C. Molecular cloning and sequence analysis of the complestatin biosynthetic gene cluster. Proc.Natl. Acad. Sci. U S A (2001), 98, 8548-8553.
  184. Tsunoda, M.; Kusakabe, Y.; Tanaka, N.; Ohno, S.; Nakamura, M.; Senda, T.; Moriguchi, T.; Asai, N.; Sekine, M.; Yokogawa, T.; Nishikawa, K.; Nakamura, K. T. Structural basis for recognition of cognate tRNA by tyrosyl-tRNA synthetase from three kingdoms. Nucleic Acids Res. (2007), 35, 4289-4300.
  185. Beau, F.; Bollet, C.; Coton, T.; Garnotel, E.; Drancourt, M. Molecular identification of a Nocardiopsis dassonvillei blood isolate. J. Clin. Microbiol. (1999), 37, 3366-3368.
  186. Majerus, P. W.; Alberts, A. W.; Vagelos, P. R. Acyl Carrier Protein. Iv. The Identification of 4'-Phosphopantetheine as the Prosthetic Group of the Acyl Carrier Protein. Proc. Natl. Acad. Sci. U S A (1965), 53, 410-417.
  187. Anke, T.; Diekmann, H. Biosynthesis of sideramines in fungi. Rhodotorulic acid synthetase from extracts of rhodotorula glutinis. FEBS Lett. (1972), 27, 259-262.
  188. Kuratani, M.; Sakai, H.; Takahashi, M.; Yanagisawa, T.; Kobayashi, T.; Murayama, K.; Chen, L.; Liu, Z. J.; Wang, B. C.; Kuroishi, C.; Kuramitsu, S.; Terada, T.; Bessho, Y.; Shirouzu, M.; Sekine, S.; Yokoyama, S. Crystal structures of tyrosyl-tRNA synthetases from Archaea. J. Mol. Biol. (2006), 355, 395-408.
  189. King, R. R.; Calhoun, L. A. The thaxtomin phytotoxins: sources, synthesis, biosynthesis, biotransformation and biological activity. Phytochemistry (2009), 70, 833-841.
  190. Waring, P.; Beaver, J. Gliotoxin and related epipolythiodioxopiperazines. Gen. Pharmacol. (1996), 27, 1311-1316.
  191. Phelan, V. V.; Du, Y.; McLean, J. A.; Bachmann, B. O. Adenylation enzyme characterization using gamma -(18)O(4)-ATP pyrophosphate exchange. Chem. Biol. (2009), 16, 473-478.
  192. Stachelhaus, T.; Mootz, H. D.; Marahiel, M. A. The specificity-conferring code of adenylation domains in nonribosomal peptide synthetases. Chem. Biol. (1999), 6, 493-505.
  193. Aravind, L.; de Souza, R. F.; Iyer, L. M. Predicted class-I aminoacyl tRNA synthetase-like proteins in non-ribosomal peptide synthesis. Biol. Direct (2010), 5, 48. References 185
  194. Hider, R. C.; Kong, X. Chemistry and biology of siderophores. Nat. Prod. Rep. (2010), 27, 637-657.
  195. Cytochrome P450-catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis. Nat. Chem. Biol. (2012), 8, 814-816.
  196. Barry, S. M.; Challis, G. L. Recent advances in siderophore biosynthesis. Curr. Opin. Chem. Biol. (2009), 13, 205-215.

* Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten
© UB Marburg 1997 - 2024 Universitätsbibliothek Marburg