The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 43 , Issue 6
Showing 1-22 articles out of 22 articles from the selected issue
  • L. D. BOECK, H. R. PAPISKA, R. W. WETZEL, J. S. MYNDERSE, D. S. FUKUDA ...
    1990 Volume 43 Issue 6 Pages 587-593
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A54145 is a complex of new lipopeptide antibiotics that inhibits Gram-positive bacteria and acts as a growth promotant for broiler chicks. Eight factors; A, B, C, D, E, F, A1 and B1; have been isolated and characterized. They contain four similar peptide nuclei, each of which is acylated with either an 2-decanoyl, n-decanoyl, or undecanoyl side chain. Taxonomic studies ascertained that the producing microorganism was a strain of Streptomyces fradiae. Fermentation studies determined that superior antibiotic yields were obtained in stirred bioreactors in a soybean flour-molasses medium employing a continuous glucose feed. These findings, interwoven with the selection of hyper-productive mutants, increased fermentation yields from <50μg/ml to more than 1 mg/ml. An analytical HPLC system was developed for the identification and subsequent quantitation of each factor of the A54145 complex.
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  • D. S. FUKUDA, R. H. DU BUS, P. J. BAKER, D. M. BERRY, J. S. MYNDERSE
    1990 Volume 43 Issue 6 Pages 594-600
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A54145 is a complex of acidic lipopeptide antibiotics which are produced by Streptomyces fradiae and are active against Gram-positive bacteria. The A54145 complex was isolated by adsorption on Diaion HP-20 nonfunctionalized macroreticular resin and/or ion exchange on Amberlite IRA-68 anion exchange resin. Antibacterial factors A, A1, B, B1, C, D, E, and F were obtained in purified form by repeated preparative reverse phase HPLC on C8 and/or C18 bonded-phase supports. The molecular formulae of the factors are C72H109N17O27 (factors A and A1), C73H111N17O27 (factors B, B1, C, and D), C74H113N17O27 (factor E), and C71H107N17O27 (factor F). The identities of the acyl side chains were established as 8-methylnonanoyl (factors F, A, and B1), n-decanoyl (factors A1 and B), and 8-methyldecanoyl (factors C, D, and E).
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  • D. S. FUKUDA, M. DEBONO, R. M. MOLLOY, J. S. MYNDERSE
    1990 Volume 43 Issue 6 Pages 601-606
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A54145 is a complex of acidic lipopeptide antibiotics produced by Streptomyces fradiae NRRL 18158, NRRL 18159, and NRRL 18160. Each antibiotic factor consists of a peptide core bearing an N-terminal acyl substituent. N-Lys-tert-BOC-protected A54145 complex was deacylated by Actinoplanes utahensis; three protected core peptides were isolated. A54145 antibiotic analogs were synthesized by acylation of the tryptophan N-terminus with 2, 4, 5-trichlorophenyl active esters, followed by deblocking with trifluoroacetic acid.
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  • L. D. BOECK, R. W. WETZEL
    1990 Volume 43 Issue 6 Pages 607-615
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A54145 is a complex of new lipopeptide antibiotics produced by Streptomyces fradiae. Eight factors, containing four similar peptide nuclei in combination with three different fatty acid acyl side chains, have been isolated from the natural fermentation and characterized. The nuclei differ only in valine/isoleucine and glutamate/3-CH3-glutamate substitutions at one or both of two locations on the peptide ring. Prior deacylation of all four nuclei with Actinoplanes utahensis had permitted chemical reacylation of each nucleus with new fatty acid acyl chains for structure-activity relationship studies. In an effort to induce the native biosynthesis of preferred factors or analogs by S. fradiae, the effect of fatty acid precursors on the fermentation was examined. Many fatty acids were extremely toxic to S. fradiae, which limited experiments to slow, continuous feeding of the lipids in stirred bioreactors that were equipped for on-line respiration analysis by mass spectrometry. These studies determined that precursing with aliphatic fatty acids of various chain lengths did enhance the biosynthesis of factors containing specific fatty acid acyl side chains. Caprate, for example, increased the n-decanoyl-containing factors from the natural level of -14% to -80%. The percentage of factors containing branched-chain fatty acid acyl substituents was also increased, in shaken-flask studies, by enriching the medium with valine or isoleucine. These amino acids additionally enhanced the percentage of nuclei containing either valine or isoleucine.
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  • F. T. COUNTER, N. E. ALLEN, D. S. FUKUDA, J. N. HOBBS, J. OTT, P. W. E ...
    1990 Volume 43 Issue 6 Pages 616-622
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A54145 complex is made up of eight factors; A, A1, B, B1, C, D, E, and F which were active in vitro (MIC 0.25- > 32μg/ml) against Gram-positive aerobic organisms. The complex, factors B and B1 were found to be active against two strains of Clostridiumperfringens. A calcium dependence study on some of the factors showed that their in vitro antibacterial activity was greatly enhanced by the presence of calcium (50 mg/liter) in the media. Resistance build-up was seen when Staphylococcus sp. and Streptococcus sp. were passed seven times in the presence of sublethal concentrations of A54145 antibiotics. This resistance disappeared immediately when the resistant organisms were passed in the absence of the antibiotics. Factor A was very effective against Staphylococcus aureus and Streptococcuspyogenes infections in mice (sc ED50s of 3.3-2.4 mg/kg × 2, respectively). Factor B was more active against S. pyogenes in vivo (sc ED50, 0.9 mg/kg × 2). Acute mouse toxicities were determined with these antibiotics. Semisynthetic derivatives were evaluated.
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  • DISCOVERY, TAXONOMY, FERMENTATION, ISOLATION, CHARACTERIZATION, AND ANTIBACTERIAL EVALUATION
    D. S. FUKUDA, J. S. MYNDERSE, P. J. BAKER, D. M. BERRY, L. D. BOECK, R ...
    1990 Volume 43 Issue 6 Pages 623-633
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    New semi-naphthaquinone antibiotics A80915A, B, C, and D were isolated from the fermented broth of Streptomyces aculeolatus A80915 (NRRL 18422). Factors A and C, present in both the broth filtrate and mycelial methanol extract, and factors B and D, found predominantly in the broth filtrate, were recovered by extraction with ethyl acetate. Purification of the individual factors was accomplished by preparative reverse phase high performance liquid chromatography on C18 bonded silica supports. Factors A-D show antimicrobial activity against Gram-positive aerobic and anaerobic organisms in vitro. Mechanism of action studies demonstrated nearly complete inhibition of macromolecular biosynthesis (protein, RNA, DNA, and cell wall) by A80915 factors A-D. A less highly cyclized semi-naphthaquinone, A80915 factor G, was isolated from the broth of the strain fermented in an alternate medium.
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  • PRODUCTION, ISOLATION, PHYSICO-CHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITIES
    AKIO SHIRAISHI, MUTSUO NAKAJIMA, TOSHIAKI KAXAYAMA, TOMOKO MAXSUDA, TA ...
    1990 Volume 43 Issue 6 Pages 634-638
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    We have constructed a new screening system for detecting microbial products that enhance host resistance against bacterial infection. It was found that a new compound with such activity is produced by a soil isolate classified as Nocardia sp. SANK 60484. The compound was isolated from the culture filtrate of the organism and named aladapcin after its amino acid composition. Aladapcin was obtained as an amphoteric white amorphous powder with the molecular formula, C13H25N5O5. It consists of 2mol of D-alanine and 1 mol of meso-diaminopimelic acid. From the analysis of IR, 1H NMR and FAB-MS spectra, the structure was assigned to be a tripeptide. Aladapcin enhanced host resistance against an experimental Escherichia coli infection in mice at doses ranging between 1 and 100μg/kg.
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  • II. AMYCINS A AND B, TWO NOVEL NIPHIMYCIN ANALOGS ISOLATED FROM A HIGH PRODUCER STRAIN OF ELAIOPHYLIN AND NIGERICIN
    SUSANNE GRABLEY, PETER HAMMANN, WOLFGANG RAETHER, JOACHIM WINK, AXEL Z ...
    1990 Volume 43 Issue 6 Pages 639-647
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Two novel natural niphimycin analogs, amycins A (5) and B (3) were isolated from the culture broth of the Streptomyces sp. DSM 3816 by chemical screening methods. In addition this strain produces the antibiotics niphimycin (4), elaiophylin (2) and nigericin (1). Fermentation, isolation, structure elucidation and biological activity of the amycins are described.
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  • W. PFEFFERLE, H. ANKE, M. BROSS, B. STEFFAN, R. VIANDEN, W. STEGLICH
    1990 Volume 43 Issue 6 Pages 648-654
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Asperfuran is a novel antifungal dihydrobenzofuran derivative produced by a strain of Aspergillus oryzae. Asperfuran weakly inhibited chitin synthase from Coprinus cinereus. This inhibition could be abolished by the addition of egg lecithin. In the agar diffusion assay asperfuran induced morphological changes in Mucor miehei at very low concentrations (20 ng/disc) while growth was only partly inhibited. In HeLa S3 and L1210 cells it showed weak cytotoxicity, the IC50 was 25 μg/ml.
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  • I. FERMENTATION, ISOLATION AND BIOLOGICAL ACTIVITY
    ANDREAS FREDENHAGEN, ANTON KUHN, HEINRICH H. PETER, VINCENZO CUOMO, UG ...
    1990 Volume 43 Issue 6 Pages 655-660
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Three new strobilurins F, G and H, antibiotics with antifungal activity, were isolated from cultures of Bolinea lutea Sacc. These new compounds differ from previously described analogs in their aromatic substitution. An HPLC method allows complete separation of all the components.
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  • II. STRUCTURE DETERMINATION
    ANDREAS FREDENHAGEN, PAUL HUG, HEINRICH H. PETER
    1990 Volume 43 Issue 6 Pages 661-667
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structures of the new antibiotics strobilurins F, G and H and of compound 8 were determined by spectroscopic methods, mainly 1H and 13C NMR and confirmed by degradation reactions.
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  • JOHN P. DIRLAM, ANNETTE M. BELTON, JON BORDNER, WALTER P. CULLEN, LIAN ...
    1990 Volume 43 Issue 6 Pages 668-679
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A new polyether antibiotic CP-84, 657 (C45H78O14) was isolated by solvent extraction from the fermentation broth of Actinomadura sp. (ATCC 53708). Following purification by column chromatography and crystallization, the structure of CP-84, 657 was elucidated by spectroscopic (NMR and MS) methods. The absolute stereochemistry was determined by a single crystal X-ray analysis of the corresponding rubidium salt. CP-84, 657 is among the most potent anticoccidal agents known, effectively controlling the Eimeria species that are the major causative agents of chicken coccidiosis at doses of 5 mg/kg or less in feed. It is also active in vitro against certain Gram-positive bacteria, as well as the spirochete, Treponema hyodysenteriae.
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  • ANDRZEJ CZERWINSKI, TERESA ZIENIAWA, EDWARD BOROWSKI, LUIGI G. MICOSSI
    1990 Volume 43 Issue 6 Pages 680-683
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The synthesis of amphotericin B 2-morpholinoethylamide diaspartate, a new water soluble antibiotic derivative with improved selective toxicity is described and in vitro biological data are presented.
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  • MIGUEL A. FERRERO, ANGEL REGLERO, JAVIER MARTIN-VILLACORTA, JOSÉ ...
    1990 Volume 43 Issue 6 Pages 684-691
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    "In vitro" synthesis of benzylpenicillin and phenoxymethylpenicillin has been carried out by direct N-acylation of 6-aminopenicillanic acid (6-APA) with S-phenylacetyl- and (S-phenoxyacetyl)glutathione. The reactions were catalyzed by the enzyme acyl-CoA: 6-APA acyltransferase (AT) from Penicillium chrysogenum and in both cases the synthesis of antibiotics was enhanced by CoA. Penicillin K, a natural penicillin, was also synthesized "in vitro" by incubating (S-octanoyl)glutathione, 6-APA and AT, but in this case the formation of antibiotic required the presence of CoA. Furthermore, benzylpenicillin was obtained from (S-phenylacetytycysteinylglycine and 6-APA, suggesting that some intermediates of the γ-glutamyl cycle are directly involved in the biosynthesis of penicillins.
    To explain "in vivo" formation of this β-lactam antibiotic, a biosynthetic pathway which includes several glutathione-S-derivatives and a non-enzymatic reaction, is proposed.
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  • HYUN Soo KIM, HIDEAKI TADA, TAKUYA NIHIRA, YASUHIRO YAMADA
    1990 Volume 43 Issue 6 Pages 692-706
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Virginiae butanolide C (VB-C) is an autoregulator which triggers virginiamycin production in Streptomyces virginiae. A new binding assay with tritium-labeled VB-C analogue (2, 3-cis-2-(1'hydroxy-[6', 7'-3H]heptyl)-3-(hydroxymethyl)butanolide) was developed and a specific VB-C binding protein was purified to homogeneity from crude extracts of S. virginiae by ammonium sulfate fractionation, DEAE-Sephacel and Sephadex G-100 column chromatographies, hydrophobic HPLC on phenyl 5PW and native polyacrylamide gel electrophoresis. The VB-C binding protein showed an apparent Mr of 35, 800 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Mr of 26, 000 - 44, 000 on native molecular sieve HPLC, indicating the monomeric nature of the binding protein. The binding protein efficiently bound to a VB affinity column and eluted specifically by VB-C, which confirmed the specific nature of the binding protein. The binding activity decreased by 40% in the presence of genomic DNA from S. virginiae, indicating interaction between the VB-C binding protein and the DNA.
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  • JEAN-JACQUES SANGLIER, RENÉ TRABER, ROBERT HELMUT BUCK, HANS HO ...
    1990 Volume 43 Issue 6 Pages 707-714
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    By mutagenic treatment of a strain of Tolypocladium inflatum, a cyclosporin non-producing mutant was obtained which accumulated the characteristic building unit of cyclosporins, (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine (abbreviation Bmt; systematic name: (2S, 3R, 4R, 6E)-2-amino-3-hydroxy-4-methyl-6-octenoic acid) in free form. The isolation from a culture filtrate was performed by extraction, chromatographic separation and final crystallization from methanol - water. The structure and stereochemistry of this amino acid was determined by chemical transformation and correlation to dihydro-MeBmt, with known chirality [(2S, 3R, 4R)-3-hydroxy-4-methyl-2-methylamino-octanoic acid], obtained by hydrolysis of dihydrocyclosporin A.
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  • YOSUKE SAWADA, KEI-ICHI NUMATA, TSUTOMU MURAKAMI, HARUMI TANIMICHI, SA ...
    1990 Volume 43 Issue 6 Pages 715-721
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Pradimicin A shows candicidal activity at 10 μg/ml in vitro. The action of pradimicin A on Candida albicans cells involves a set of specific cell surface interactions in a Ca2+-dependent manner. These include binding to the mannan components on the cell surface and subsequent interactions at the level of the plasma membrane, causing K+ leakage and cell death. The protoplasts prepared from C. albicans undergo lysis rapidly when treated with pradimicin A. These results suggest that pradimicin A acts primarily on the candidal plasma membrane, leading to a perturbation of membrane function.
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  • NAOKI ASANO, MASAYOSHI TAKEUCHI, YUKIHIKO KAMEDA, KATSUHIKO MATSUI, YO ...
    1990 Volume 43 Issue 6 Pages 722-726
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Validoxylamine A showed a potent inhibitory activity against insect trehalase in a competitive manner with a Ki value of 4.3 × 10-10 M. The other validoxylamines and validamycins also exhibited the activity in vitro. Injection of these compounds to young last instar larvae of the tobacco cutworm, Spodoptera litura, elicited the morphological abnormality followed by death after the cessation of feeding. Validoxylamine A showed 100% mortality at a dose of 10 μg/ last instar larva.
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  • JOHN P. DIRLAM, LAURA PRESSEAU-LINABURY, DAVID A. KOSS
    1990 Volume 43 Issue 6 Pages 727-730
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • EDWARD KATZ, HELEN A. LLOYD, ANTHONY B. MAUGER
    1990 Volume 43 Issue 6 Pages 731-733
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • WOLFRAM KÖLLER, FRANCES TRAIL, DIANA M. PARKER
    1990 Volume 43 Issue 6 Pages 734-735
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • REZSÖ BOGNÁR
    1990 Volume 43 Issue 6 Pages 737-738
    Published: June 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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