The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 55 , Issue 3
Showing 1-14 articles out of 14 articles from the selected issue
  • Fermentation, Isolation, Structure Elucidation and Biological Activities
    KAZUYUKI MINAGAWA, SHUICHI KOUZUKI, HIROYOSHI TANI, KIKUO ISHII, TATSU ...
    2002 Volume 55 Issue 3 Pages 239-248
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Stachybotrys sp. RF-7260 was found to produce stachyflins, novel anti-influenza virus agents, under solid-state fermentation conditions. Feeding DL-lysine to a culture of Stachybotrys sp. RF-7260 induced the formation of the novel compounds, SQ-02-S-L2 and -L1, and feeding DL-valine the formation of SQ-02-S-V1 and -V2. The structures of these metabolites were determined by detailed 2D NMR analyses in comparison with acetylstachyflin. SQ-02-S-L2 and -L1 have the lysine moiety and SQ-02-S-V1 has the valine moiety. SQ-02-S-V2 has an amidine moiety instead of the lactam moiety in acetylstachyflin. SQ-02-S-L2, -L1 and -V1, substituted on the lactam amide hydrogen, displayed only a low level of the antiviral activity. However, deacetyl SQ-02-S-V2 showed potent antiviral activity similar to stachyflin.
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  • TOMOMITSU SASAKI, YASUHIRO IGARASHI, NORIKO SAITO, TAMOTSU FURUMAI
    2002 Volume 55 Issue 3 Pages 249-255
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Two novel antibiotics, watasemycins A and B, were isolated from the fermentation broth of an actinomycete strain. The producing strain TP-A0597 was isolated from the seawater sample collected in Toyama Bay, Japan and identified as Streptomyces sp. based on the taxonomic study. The new antibiotics were obtained by solvent extraction and chromatographic purification and spectroscopic analyses identified that they were new analogs of thiazostatins. Watasemycin possesses a methyl group at 5'-position of thiazostatin instead of a hydrogen atom. Watasemycins showed antibiotic activity against Gram-positive and negative bacteria and yeast.
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  • SHIORI MEGURO, MICHIO NAMIKOSHI, HISAYOSHI KOBAYASHI
    2002 Volume 55 Issue 3 Pages 256-262
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    A new screening method to detect antimitotic substances utilizing purified porcine brain microtubule proteins was developed. This method observes the inhibitory and stimulatory activities on microtubule polymerization and inhibitory activity on depolymerization in sequence. Two glycolipids, 1-O-β-D-galactopyranosyl-2, 3-di-O-acylglycerol and 1-O-tetrahydroxycyclopentyl-2-O-acyl-3-O-alkylglycerol were isolated from Okinawan marine sponge Pseudoceratina sp. by this screening method. These compounds stimulated the microtubule polymerization at 10°C.
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  • YASUMASA SUGIYAMA, HIROMICHI NAGASAWA, AKINORI SUZUKI, SHOHEI SAKUDA
    2002 Volume 55 Issue 3 Pages 263-269
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Trehazolin (1) is a trehalase inhibitor produced by Micromonospora coriacea. Biosynthesis of 1 was studied by feeding experiments with a variety of labeled precursors. Feeding experiments with [1-13C]- and [6-13C]-D-glucose revealed that the carbon skeletons of both a glucose residue and a cyclopentane ring moiety in 1 were each derived from glucose, and that C-C bond formation between C-1 and C-5 of glucose occurred during the cyclopentane ring formation. Furthermore, an experiment with [guanidino-13C, 15N2]-L-arginine revealed that two nitrogen atoms and a quaternary carbon atom involved in the aminooxazoline moiety of 1 originated from an amidino group of arginine. Further feeding experiments with [1-2H]-, [2-2H]-, [4-2H]-, [6, 6-2H2]- and [1, 2, 3, 4, 5, 6, 6-2H7]-D-glucose as well as [1-13C]-D-fructose showed that deuteriums on C-1, C-3, C-4 and C-6 of glucose were retained during the formation of the cyclopentane ring moiety of 1.
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  • SUNG IG CHO, HIDESUKE FUKAZAWA, YOSHIO HONMA, TAKAYUKI KAJIURA, HIROSH ...
    2002 Volume 55 Issue 3 Pages 270-278
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    We studied the effects of hibarimicins and hibarimicin-related compounds produced by Microbispora rosea subsp. hibaria [glycosides (hibarimicins A, B, C, D, E, G, H and I) and aglycon (hibarimicinone)] or compounds produced by its mutants [glycosides (HMP-P4 and -Y6), aglycons (HMP-P1 and -Y1) and shunt products (HMP-M1, M2, M3 and -M4)] on v-Src tyrosine kinase and growth and differentiation of human myeloid leukemia HL-60 cells. Among them, hibarimicin B was a strong and the most selective v-Src kinase inhibitor with differentiation inducing activity of HL-60 cells. Hibarimicin E similarly induced HL-60 cell differentiation but had no v-Src kinase inhibitory activity. Hibarimicinone was the most potent v-Src kinase inhibitor, although less selective, and did not induce differentiation of HL-60 cells. Hibarimicin B competitively inhibited ATP binding to the v-Src kinase, but hibarimicinone showed noncompetitive inhibition. These two compounds, however, showed similar mixed types of inhibition against a Src substrate binding to the v-Src kinase. Altogether, these results suggest that signaling molecules other than Src might be more important in the differentiation induction of HL-60 cells.
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  • DONGYU SUN, SETH COHEN, NAGRAJ MANI, CHRIS MURPHY, DAVID M. ROTHSTEIN
    2002 Volume 55 Issue 3 Pages 279-287
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    A pathway-specific cell-based screen is described to detect compounds that inhibit the biosynthesis of the cell wall of bacteria. The basis for detection is the discovery that the β-lactamase gene from Citrobacter freundii, cloned into Escherichia coli, is induced when cells are exposed to known cell wall inhibitors, and not just β-lactam-based antibiotics. In a wild type host, cell wall inhibitors such as moenomycin, vancomycin, and ramoplanin, which are excluded by the outer membrane, only induce at high concentrations. However, these compounds, as well as fosfomycin, cycloserine, and cefoxitin, induce at concentrations at or below the MIC of a host carrying the envA-mutation, which causes a defect in the outer membrane. As additional proof that induction of β-lactamase is the direct result of cell wall inhibition, a host strain carrying a temperature-sensitive mutation in the murG gene, whose product converts the cell wall intermediate Lipid I, to Lipid II, also induced β-lactamase at the restrictive temperature. A protocol is described for screening samples in high-throughput mode.
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  • MAUREEN DECENZO, MIKE KURANDA, SETH COHEN, JOHN BABIAK, ZHI-DONG JIANG ...
    2002 Volume 55 Issue 3 Pages 288-295
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    A screening system is described that can detect and confirm inhibitors of the late steps of cell wall biosynthesis. The primary high through-put screen monitors induction of β-lactamase following exposure to samples, in an Escherichia coli envA- strain that carries the β-lactamase gene from Citrobacter freundii on a plasmid. Positive samples were detected from compound libraries, from natural products libraries, and from fractions of natural products crude preparations. These samples were then subjected to in vitro assays that could detect the incorporation of soluble cell wall precursor into Lipid I, Lipid II, and polymerized cell wall, using a TLC system that was very accurate and unambiguous in detecting known cell wall inhibitors. One partially purified sample containing a novel antibacterial agent derived from natural products was found to inhibit the formation of Lipid I (50% inhibition at ≤62.5ng/ml), whereas another partially purified sample also derived from natural products inhibited transglycosylation into cell wall polymer (50% inhibition at ≤10μg/ml). This screening system proved to be especially useful because it was sufficiently sensitive and robust to detect inhibitors among samples of crude preparations or varying states of purity.
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  • II. Determination of Chemical Structure
    YASUAKI ESUMI, YOSHIKATSU SUZUKI, YUMIKO ITOH, MASAKAZU URAMOTO, KEN-I ...
    2002 Volume 55 Issue 3 Pages 296-300
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    The structure of propeptin, a new inhibitor of prolyl endopeptidase isolated from Microbispora sp. SNA-115, was determined. FAB/MS, Edman degradation and amino acid analysis revealed propeptin to be a cyclic polypeptide consisting of 19 common L-amino acids. By FAB/MS and protein chemical methods, the primary sequence of propeptin was determined to be Gly1-Tyr-Pro-Trp-Trp-Asp-Tyr-Arg-Asp9-Leu-Phe-Gly-Gly-His-Thr-Phe-Ile-Ser-Pro19, which cyclizes between the β-carboxyl group of Asp9 and the α-amino group of Gly1.
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  • II. Structure Elucidation and Biosynthesis
    MEIKE HOLZENKÄMPFER, MARTINA WALKER, AXEL ZEECK, JUDITH SCHIMANA, ...
    2002 Volume 55 Issue 3 Pages 301-307
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    The simocyclinones D4 (1) and D8 (2), members of a novel class of antibiotics, were isolated from the mycelial extract of Streptomyces antibioticus Tü 6040 and consist of angucyclinone, deoxysugar, octatetraene dicarboxylate and aminocoumarin structural elements. The structure elucidation was done by one and two dimensional NMR experiments, and other spectroscopic methods in combination with incorporation experiments using 13C labelled precursors.
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  • MARIJANA HRANJEC, KRISTINA STARCEVIC, BRANIMIR ZAMOLA, STJEPAN MUTAK, ...
    2002 Volume 55 Issue 3 Pages 308-314
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    New amidino-benzimidazolyl derivatives of antibiotics tylosin and desmycosin are prepared in the reaction of corresponding amidino-substituted o-phenylendiamine with tylosin respectively desmyicosin on the 20-C aldehyde group. The reaction was carried out in absolute ethanol in the presence of p-benzoquinone. On this way are prepared:
    20-[5-(N-isopropylamidino)-2-benzimidazolyl]tylosin hydrochloride 9, 20-[5-(2-imidazolinyl)-2-benzimidazolyl]tylosin hydrochloride 10, 20-[5-(N-morpholinylamidino)-2-benzimidazolyl] tylosin hydrochloride 11, 20-[5-(N-isopropylamidino)-2-benzimidazolyl]desmycosin hydrochloride 12, 20-[5-(2-imidazolinyl)-2-benzimidazolyl]desmycosin hydrochloride 13, 20-[5-(N-morpholinylamidino)-2-benzimidazolyl]desmycosin hydrochloride 14.
    Their antimicrobial activity was tested on a series of microorganisms.
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  • VII. Membrane Injury Induced by C9-UK-2A, a Derivative of UK-2A, in Rhodotorula mucilaginosa IFO 0001
    KAZUNORI TANI, YOSHINOSUKE USUKI, KAZUHIKO MOTOBA, KEN-ICHI FUJITA, MA ...
    2002 Volume 55 Issue 3 Pages 315-321
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    UK-2A is a potent antifungal antibiotic and its structure is highly similar to that of antimycin A3 (AA). UK-2A and AA inhibit mitochondrial electron transport at complex III. However, the antifungal activities of UK-2A and AA disappear after 48-hour treatment. In an attempt to improve the duration of the antifungal activity of UK-2A, several UK-2A derivatives were prepared by substituting its nine-membered dilactone ring with an n-alkyl or an isoprenyl moiety. Among all the derivatives tested, C9- and C10-UK-2A showed the most potent and durable antifungal activities against a strict aerobic yeast, Rhodotorula mucilaginosa IFO 0001. C9-UK-2A, in particular, continued to demonstrate its broad-spectrum antifungal activity after 120-hour treatment. Therefore, we focused on C9-UK-2A to further examine its mode of action against the yeast. Interestingly, C9-UK-2A did not inhibit cellular respiration of the cells even at concentrations greater than 100μg/ml. C9-UK-2A gradually induced the efflux of potassium ions from the cells. Moreover, C9-UK-2A gradually induced the release of glucose from glucose-encapsulating liposomes. The patterns of efflux and release induced by C9-UK-2A were not as rapid as those seen with amphotericin B. These results suggest a membrane injury caused by C9-UK-2A in R. mucilaginosa IFO 0001.
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  • I. Structure-activity Relationships on the Terminal Peptidic Moiety
    ATSUSHI HASUOKA, YUJI NISHIKIMI, YUTAKA NAKAYAMA, KEIJI KAMIYAMA, MASA ...
    2002 Volume 55 Issue 3 Pages 322-336
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    The novel natural antibiotics pyloricidin A, B and C possess potent and highly selective antibacterial activity against Helicobacter pylori. In order to investigate the structure activity relationships for the terminal peptidic moiety, a series of pyloricidin B and pyloricidin C derivatives, bearing various amino acids in the moiety, were prepared and evaluated for their anti-H. pylori activity. The derivatives bearing α-D-, β- and γ-amino acids or peptidemimetics showed drastically decreased activity. On the other hand, the derivatives with α-L-amino acids were found to maintain the activity. Among the derivatives prepared in this work, the allylglycine derivative 2s showed the most potent anti-H. pylori activity, with an MIC value of less than 0.006μg/ml against H. pylori NCTC11637, which is 60-fold greater than the activity of the lead compound pyloricidin C.
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  • YOSHIYUKI TAKAYASU, KOUICHI TSUCHIYA, YOSHIKAZU SUKENAGA
    2002 Volume 55 Issue 3 Pages 337-340
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
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  • MEIKE HOLZENKÄMPFER, AXEL ZEECK
    2002 Volume 55 Issue 3 Pages 341-342
    Published: March 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
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