The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 46, Issue 3
Displaying 1-23 of 23 articles from this issue
  • MASAHISA OKA, SEIJI IIMURA, OSAMU TENMYO, YOSUKE SAWADA, MASARU SUGAWA ...
    1993 Volume 46 Issue 3 Pages 367-373
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Terpestacin, a new antibiotic which inhibits syncytium formation, was isolated from Arthrinium sp. FA1744 (ATCC 74132). The structure of terpestacin was elucidated as a bicyclic sesterterpene on the basis of spectroscopic data and chemical derivatization.
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  • I. TAXONOMY AND FERMENTATION OF THE PRODUCING ORGANISM AND BIOLOGICAL ACTIVITY
    JAMES P. KARWOWSKI, MARIANNA JACKSON, RONALD R. RASMUSSEN, PATRICK E. ...
    1993 Volume 46 Issue 3 Pages 374-379
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    The ardeemins are a new family of secondary metabolites produced by submerged fermentation of a fungus which was isolated from a soil sample collected in Brazil. Based on taxonomic studies, the producing culture was identified as Aspergillus fischeri var. brasiliensis strain AB 1826M-35. 5-N-Acetylardeemin potentiated the cytotoxicity of the anticancer agent vinblastine in multidrug resistant human tumor cells.
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  • II. ISOLATION AND ELUCIDATION OF THE STRUCTURE OF 5-N-ACETYLARDEEMIN AND TWO CONGENERS
    JILL E. HOCHLOWSKI, MARK M. MULLALLY, STEPHEN G. SPANTON, DAVID N. WHI ...
    1993 Volume 46 Issue 3 Pages 380-386
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    A family of novel compounds has been detected and isolated following an assay for the attenuation of multiple drug resistance in tumor cells from the fermentation broth and mycelia of a strain of Aspergillus fischeri which we have designated var. brasiliensis. The structures of three components were determined employing 1-D and 2-D homonuclear and heteronuclear NMR spectroscopy and mass spectrometry. The structure of 5-N-acetylardeemin was confirmed by single crystal X-ray diffraction. These compounds are most closely structurally related to asnerlicin E1)
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  • KYOICHIRO SAITOH, YOSUKE SAWADA, KOJI TOMITA, TAKASHI TSUNO, MASAMI HA ...
    1993 Volume 46 Issue 3 Pages 387-397
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Pradimicin L, a new congener of pradimicin A having the D-glucosyl-D-thomosamine moiety at the C-5 position, was isolated from Actinomadura verrucosospora subsp. neohibisca subsp. nov. The structure of pradimicin L was deduced to be N-[[(5S, 6S)-5-O-[4, 6-dideoxy-4-(methylamino)-3-O-(β-D-glucopyranosyl)-β-D-galactopyranosyl]-5, 6, 8, 13-tetrahydro-1, 5, 6, 9.14-pentahydroxyll-methoxy-3methyl-8, 13-dioxobenzo[a]naphthacene-2 yl]carthonyl]-D-alanime by MS and NMR spectrometry and degradation studies. Pradimicin FL which has the D-serine moiety instead of D-alanine was produced by directed biosynthesis in D-serine-supplemented medium. Pradimicins L and FL have a broad spectrum of in vitro antifungal activity. Pradimicin L was equiactive to pradimicin A and pradimicin FL was more active than pradimicin L.
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  • KYOICHIRO SAITOH, KIYOSHI SUZUKI, MINORU HIRANO, TAMOTSU FURUMAI, TOSH ...
    1993 Volume 46 Issue 3 Pages 398-405
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Exogenous addition of D-serine to Actinomadura spinosa AA0851 resulted in directed production of pradimicin FS, a new D-serine analog of pradimicin S, together with pradimicin FB. Pradimicin FS was produced in higher yields by derivation of ferrous sulfate-resistant strains from strain AA0851. Pradimicin FB, a minor product, was identified as deglucosylpradimicin FL. Pradimicin FS was equivalent to pradimicin S in syncytium formation inhibition activity and in vitro and in vivo antifungal activities.
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  • II. ISOLATION AND STRUCTURE ELUCIDATION
    KYOICHIRO SAITOH, TAKASHI TSUNO, MASATOSHI KAKUSHIMA, MASAMI HATORI, T ...
    1993 Volume 46 Issue 3 Pages 406-411
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Pradimicin S was isolated from the culture nitrate of Actinomadura spinosa AA0851. NMR and MS analyses proved that pradimicin S is the 3'-O-(3"-O-sulfo-β-D-glucopyranosyl) analog of pradimicin A, a new member of the pradimicin family of antibiotics. Stereochemical assignment was made by correlating pradimicin S with pradimicin L.
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  • I. GENERATION AND SELECTION OF PRADIMICIN-NONPRODUCING MUTANTS
    TAMOTSU FURUMAI, SHIZUKO KAKINUMA, HARUAKI YAMAMOTO, NOBUJIRO KOMIYAMA ...
    1993 Volume 46 Issue 3 Pages 412-419
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Germinated spores of Actinomadura verrucosospora subsp. neohibisca E-40, a high pradimicins producer, were mutagenized by N-methyl-N'-nitro-N-nitrosoguanidine and/or UV treatment. Thirty-seven mutants which did not produce pradimicin were selected to test for cosynthesis ability, and classified into nine classes. On the basis of their cosynthesis ability and bioconversion results, we concluded that strain JN-213 (class III) was a true converter and that strains JN-219 (class IV), JN-47 (class V) and JNU-46 (class VI) were secretors accumulating biosynthetic intermediates of pradimicin, and that strains JN-59 (class VII), JN-58 (class VIII) and JN-207 (class IX) were producers of shunt metabolites of pradimicin biosynthesis. TLC and HPLC analyses of the fermentation broths of individual strains showed that 8 new compounds were produced along with pradinone I, pradimicinone I, 11-O-demethylpradimicinone II and 7-O-methylpradimicinone II.
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  • II. FERMENTATION, ISOLATION AND STRUCTURE DETERMINATION OF METABOLITES ASSOCIATED WITH THE PRADIMICINS BIOSYNTHESIS
    TAKASHI TSUNO, HARUAKI YAMAMOTO, YUKIO NARITA, KIYOSHI SUZUKI, TOSHIFU ...
    1993 Volume 46 Issue 3 Pages 420-429
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Ten metabolites produced by 4 mutants derived from Actinomadura verrucosospora subsp. neohibisca E-40, a high pradimicins producer, were isolated and their structures were determined. Strain JN-219 produced 3 novel analogs of the pradimicin A aglycone, i.e. 11-O-demethyl-7-methoxypradinone II and 11-O-demethylpradinones I and II together with a known aglycone analog, pradinone I, while the metabolites from strain JN-47 were determined to be 2 new aglycone analogs, 11-O-demethylpradimicinone I and 11-O-demethyl-7-methoxypradimicinone II and a known aglycone analog, 11-O-demethylpradimicinone II (11dM-PMN II). Products of strain JN-207 were identified as 11-O-demethyl-6-deoxypradinone I and 11dM-PMN II. Interestingly, a new pradimicin analog, 7-hydroxypradimicin A was isolated from strain JN-58 together with a new aglycone analog, pradimicinone II and 11dM-PMN II. None of these metabolites showed antifungal activity.
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  • III. BIOSYNTHETIC PATHWAY OF BOTH PRADIMICINS AND BENANOMICINS
    SHIZUKO KAKINUMA, KIYOSHI SUZUKI, MASAMI HATORI, KYOICHIRO SAITOH, TOS ...
    1993 Volume 46 Issue 3 Pages 430-440
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    The biosynthetic pathway of the pradimicin-benanomicin family of antibiotics was investigated by using sinefungin and blocked mutants derived from Actinomadura verrucosospora subsp. neohibisca E-40 (a high pradimicin producer) or Actinomadura sp. AB1236 (a benanomicin producer). Addition of sinefungin to strain E-40, pradimicin A aglycone-producing mutant or strain AB1236 inhibited the formation of 11-O-demethyl-7-methoxypradinone II (11dM-7M-PN II), resulting in the accumulation of 11-O-demethylpradimicinone II and pradimicinone II. By feeding pradimicin A aglycone and its analogs to mutants blocked early in pradimicin or benanomicin biosynthesis, the following results were obtained: 11-O-demethylpradinone II, 11dM-7M-PN II, 11-O-demethylpradinone I, 11-O-demethylpradimicinone I and pradimicinone I were converted to pradimicin A or benanomicin A; the remaining 6 aglycone analogs were not incorporated into the antibiotics. Pradimicin B, dexylosylpradimicin C and dexylosylbenanomicin A were converted to pradimicin A, pradimicin C and benanomicin A, respectively. A biosynthetic pathway for the antibiotics is proposed.
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  • SIRI RAM CHHABRA, PAUL STEAD, NIGEL J. BAINTON, GEORGE P. C. SALMOND, ...
    1993 Volume 46 Issue 3 Pages 441-454
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    N-(3-Oxohexanoyl)-L-homoserine lactone (HSL) (I) is the autoregulator controlling carbapenem antibiotic biosynthesis in Erwinia carotovora ATCC 39048. The chemical synthesis and biological evaluation of analogues of HSL are described. These include alterations of chirality, side-chain modifications, ring size and ring hetero atom. A number of compounds are reported which are capable of restoring the phenotype to a HSL negative mutant but at higher concentrations than HSL.
    A-factor, the autoregulator of streptomycin biosynthesis in Streptomyces griseus, was not active as an inducer of carbapenem biosynthesis in E. carotovora.
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  • II. D-MANNOPYRANOSIDE-BINDING SITE AND CALCIUM-BINDING SITE
    TOMOKAZU UEKI, KEI-ICHI NUMATA, YOSUKE SAWADA, MAKI NISHIO, HIROAKI OH ...
    1993 Volume 46 Issue 3 Pages 455-464
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Based on the structure-activity relationship data of BMY-28864 and related pradimicin derivatives, the calcium salt-forming ability and the D-mannopyranoside-specific visible absorption maximum shift of BMY-28864 were analysed in the ternary complex forrnation of BMY-28864 with D-mannopyranoside and calcium. The free C-18 carboxyl group of BMY-28864 was proved to be the sole site for binding to calcium, while no hydroxyl groups of the aglycone were involved in calcium salt formation. The stereo specific D-mannopyranoside-recognizing ability of BMY-28864 was completely abolished by removal of the C-5 disaccharide moiety, and, more particularly, of the C-5 thomosamine moiety. Close relationship of these findings with the antifungal action was also supported by the in vitro antifungal assay and the potassium leakage induction test.
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  • III. SPECTROPHOTOMETRIC SEQUENCE ANALYSIS OF THE TERNARY COMPLEX FORMATION OF BMY-28864 WITH D-MANNOPYRANOSIDE AND CALCIUM
    TOMOKAZU UEKI, MASAHISA OKA, YASUO FUKAGAWA, TOSHIKAZU OKI
    1993 Volume 46 Issue 3 Pages 465-477
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Sequence of reactions in the process of ternary complex formation of BMY-28864 with D-mannopyranoside and calcium was spectrophotometrically determined under more strict analytical conditions using metal-free preparations of sugars and the pradimicin derivative at a bandpass slit width of 1 nm. In the first phase of ternary complex formation, BMY-28864 stereo specifically recognized and bound to D-mannopyranoside in the absence of calcium, which was revealed by a visible absorption maximum shift of ca. 8 nm. Subsequently, the BMY-28864-D-mannopyranoside conjugate reacted with calcium to yield the ternary complex, which was detected by an additional visible absorption maximum shift of ca. 8 nm. When the three components were mixed at the same time, both phases simultaneously occurred to produce the ternary complex which was accompanied by a visible absorption maximum shift of 16nm in total. Based on this two-phased reaction sequence, the mechanism of ternary complex formation .of BMY-28864 with D-mannopyranoside and calcium was reexamined in details. Terminal D-mannopyranoside was confirmed to be essential as BMY-28864-specific sugar receptor by in vitro analysis and animal cell experiments. While calcium, strontium and cadmium behaved similar in the in vitro ternary complex formation, the yeast and animal cell experiments showed that only calcium played a dual role as a base in the ternary complex formation and as an effector in physiological disturbances leading to cell death.
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  • KIKUTAROU ENDOU, MAYUMI MATSUOKA, HIROFUMI TANIGUCHI, YOSHINORI NAKAJI ...
    1993 Volume 46 Issue 3 Pages 478-485
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    In a previous paper we reported that rokitamycin (RKM) which killed some types of RKM-susceptible staphylococci bound cohesively to ribosomes obtained from such bacteria whereas other macrolides such as erythromycin and josamycin, which are generally known to be bacteriostatic, bound to these ribosomes only reversibly. From this observation, we speculated that such cohesive binding of RKM to certain ribosomes probably resulted in cell killing (ENDOU, K. et al., FEMS Microbiology Letters, 72: 93-96, 1990). However, this speculation was based only on circumstantial evidence and we did not show directly that reversible binding of RKM to ribosomes from other strains would bring about bacteriostasis only. A clinically isolated strain, Staphylococcus aureus S704, was found to be susceptible to RKM, mycinamicin and tylosin as well as lincosamide and streptogramin type B antibiotics but not to other macrolides (erythromycin, josamycin, rosamicin, etc.). RKM showed bacteriostatic, but not bactericidal activity, on the strain. Determinant(s) responsible for the bacteriostatic phenotype was transferred into strain NCTC8325 using bacteriophage 80L2; the obtained transductant was referred to as strain 8325MMT7. The drug bound reversibly, not cohesively, to the ribosomes from both strains S704 and 8325MMT7, confirming our earlier hypothesis that rokitamycin can cause bacteriostasis or cell death depending upon whether it binds reversibly or cohesively to the ribosomes of a given strain.
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  • ANDREW W. TAYLOR, BENJAMIN J. COSTELLO, PAMELA A. HUNTER, WILLIAM S. M ...
    1993 Volume 46 Issue 3 Pages 486-493
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
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    The syntheses of the first amphotericin B derivatives to be modified solely at the C-13 hemiketal position are described. Selective functionalisation at this position is facilitated by use of the allyl ester as a C-16 carboxylate protecting group on the amphotericin B nucleus. In in vitro tests all compounds showed markedly reduced haemolytic activity against mammalian erythrocytes while two of the novel 13-alkoxy derivatives retained good antifungal activity.
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  • MAKI NISHIO, HIROAKI OHKUMA, MASATOSHI KAKUSHIMA, SHIN-ICHI OHTA, SEUI ...
    1993 Volume 46 Issue 3 Pages 494-499
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
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    Chemical modifications of the carboxyl group in the alanine moiety of pradimicin A were performed and in vitro and in vivo antifungal activities of the derivatives were examined in comparison with those of pradimicin A. The amide derivatives showed activities comparable to pradimicin A, indicating that the free carboxyl group can be modified without impairing the antifungal activity.
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  • SATSUKI OKUYAMA, MASATOSHI KAKUSHIMA, HAJIME KAMACHI, MASATAKA KONISHI ...
    1993 Volume 46 Issue 3 Pages 500-506
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
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    A series of pradimicin analogs were designed and synthesized to investigate the effect of the amino acid side chain on the antifungal activity. The alanine-exchanged analogs (3a-3q) were synthesized from 4'-N-Cbz-pradimic acid by coupling with appropriate amino acids or their equivalents followed by deblocking. All the D-α-amino acid derivatives except D-proline analog, 3k retained the antifungal activity.
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  • YOSUKE SAWADA, TAKASHI TSUNO, TOMOKAZU UEKI, HARUAKI YAMAMOTO, YASUO F ...
    1993 Volume 46 Issue 3 Pages 507-510
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • TOSHIO OHTA, MAMORU HASEGAWA
    1993 Volume 46 Issue 3 Pages 511-517
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
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  • KEIKO NAKAGAWA, KAZUO SATO, YOSHIHISA TSUKAMOTO, AKIO TORIKATA
    1993 Volume 46 Issue 3 Pages 518-519
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • HIROSHI NAGAI, YUZURU MIKAMI, KATSUKIYO YAZAWA, TOHRU GONOI, TAKESHI Y ...
    1993 Volume 46 Issue 3 Pages 520-522
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • PETER HAMMANN, WOLFGANG RAETHER, LASZLO VERTESY
    1993 Volume 46 Issue 3 Pages 523-525
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • JOHN E. MCCULLOUGH, MARK T. MULLER, ALISON J. HOWELLS, ANTHONY MAXWELL ...
    1993 Volume 46 Issue 3 Pages 526-530
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • SHINICHI KONDO, SEIJI SHIBAHARA, TAKAYUKI USUI, TOSHIAKI KUDO, ATUSHI ...
    1993 Volume 46 Issue 3 Pages 531-534
    Published: March 25, 1993
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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