The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 37 , Issue 5
Showing 1-24 articles out of 24 articles from the selected issue
  • WILLIAM L. PARKER, MARLENE L. RATHNUM, VERA SEINER, WILLIAM H. TREJO, ...
    1984 Volume 37 Issue 5 Pages 431-440
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Two new acetylenic antibiotics, cepacins A and B, have been isolated from the fermentation broth of Pseudomonas cepacia SC 11, 783 and assigned structures 1 and 2. Cepacin A has good activity against staphylococci (MIC 0.2 μg/ml) but weak activity against streptococci (MIC 50 μg/ml) and the majority of Gram-negative organisms (MIC values 6.3->50μg/ml). Cepacin B has excellent activity against staphylococci (MIC <0.05 μg/ml) and some Gram-negative organisms (MIC values 0.1->50 μg/ml).
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  • KARL H. MICHEL, LAVERNE D. BOECK, MARVIN M. HOEHN, NOEL D. JONES, MICH ...
    1984 Volume 37 Issue 5 Pages 441-445
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structure of antibiotic A33853, isolated from the culture broth ofStreptomyces sp., NRRL 12068, is reported. The structure was deduced from an X-ray crystallographic study of its tetraacetyl derivative. Tetraacetyl A33853 is unique because it contains an anhydride moiety, an unexpected product from the reaction of A33853 with acetic anhydride and pyridine.
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  • LAVERNE D. BOECK, FREDERICK P. MERTZ, ROBERT K. WOLTER, CALVIN E. HIGG ...
    1984 Volume 37 Issue 5 Pages 446-453
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A novel vancomycin analog, N-demethylvancomycin, is produced by a soil isolate collected in Yucatan, Mexico. Taxonomic studies indicated this microorganism, designated NRRL 15232, is a strain of Nocardia orientalis. Unlike some glycopeptide antibiotics, virtually none of the N-demethylvancomycin synthesized remained bound to the cells of the producing culture. Antibiotic production was markedly depressed by the addition of orthophosphate to the fermentation medium. Enrichment of the medium with tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylic acid, or leucine, all putative precursors of the aglycone, stimulated the biosynthesis of N-demethylvancomycin.
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  • B. KUNZE, T. KEMMER, G. HÖFLE, H. REICHENBACH
    1984 Volume 37 Issue 5 Pages 454-461
    Published: 1984
    Released: April 19, 2006
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    An antibiotic activity was extracted from the cell mass of the myxobacterium, Stiginatella aurantiaca strain Sg a15. The antibiotic was toxic for yeasts and filamentous fungi, but not for most bacteria. The compound had the molecular formula C30H42O7, appears to be a new antibiotic, and was named stigmatellin. In addition to stigmatellin, the strain produced relatively large quantities of a second, structurally unrelated antibiotic, a mixture of three myxalamid homologues.
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  • LEEYUAN HUANG, GERALD ROWIN, JOSEPH DUNN, RUTH SYKES, ROBERT DOBNA, BE ...
    1984 Volume 37 Issue 5 Pages 462-465
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    L-681, 176, an inhibitor of angiotensin converting enzyme was found in the culture filtrate of Streptomyces sp. MA 5143. The I50 of the crystalline inhibitor is about 1.3μg/ml and the inhibition is reversed by zinc sulfate. In rats, L-681, 176 exhibits a dose-related inhibition of the pressor response to angiotensin I with an ID50 of 142 mg/kg when administered intravenously. The structure of L-681, 176 is similar to that of marasmine but lacking one carboxyl group. The maximum yield of L-681, 176 occurs after three to four days growth at 28°C.
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  • OTTO D. HENSENS, JERROLD M. LIESCH
    1984 Volume 37 Issue 5 Pages 466-468
    Published: 1984
    Released: April 19, 2006
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    L-681, 176 (1, C12H23N5O7) is an inhibitor of angiotensin converting enzyme produced by Streptomyces sp. MA 5143a. The structure of L-681, 176 has been determined by NMR and mass spectral analysis.
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  • KAZUYOSHI UMEHARA, KEIZO YOSHIDA, MASANORI OKAMOTO, MORITA IWAMI, HIRO ...
    1984 Volume 37 Issue 5 Pages 469-474
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    WF-5239 was produced by a fungal strain identified as Aspergillus fumigatus Fresenius. The substance was purified by solvent extraction followed by chromatography on silica gel and then crystallized (C9H9NO2, mp 142-145°C). The chemical structure was determined from its physico-chemical properties as N-[2-cis(4-hydroxyphenyl)ethenyl]formamide. WF-5239 has inhibitory activity against rabbit platelet aggregation induced by arachidonic acid and collagen, with IC50 values of 1.25 and 5.0μg/ml, respectively. Arachidonic acid induced mortality in mice was reduced by a single intraperitoneal dose of WF-5239 (30 mg/kg).These biological properties have been compared with those of aspirin.
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  • AKIRA HIROTA, MASAHIRA NAKAGAWA, HEIICHI SAKAI, AKIRA ISOGAI
    1984 Volume 37 Issue 5 Pages 475-478
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Assignment of the fifteen carbons of terrecyclic acid A, C15H20O3, a new sesquiterpene antibiotic, in the 13C NMR spectrum was performed by 13C-{1H} selective proton decoupling experiments, comparison with spectra of its derivatives and chemical shifts.
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  • KIMIHIRO WATANABE, TAMOTSU FURUMAI, MASAYUKI SUDOH, KAZUTERU YOKOSE, H ...
    1984 Volume 37 Issue 5 Pages 479-486
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Taxonomic characteristics of strains NR-320-OM7HB and NR-320-OM7HBS producing a homologous series of new α-amylase inhibitors named trestatins are described, together with the comparison of these strains with similar Streptomyces species by DNA-DNA hybridization. A new species, Streptomyces dimorphogenes sp. nov. Watanabe and Maruyama is proposed as a result of the studies. The type strain of this species is strain NR-320-OM7HB (ATCC 31484), and the morphovar is strain NR-320-OM7HBS (ATCC 31485). The productivity of trestatin A, major and most active component, using these two strains in flask culture is also presented.
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  • MIKIKO ITO-KAGAWA, YASUO KOYAMA, SHIGEJI KONDO
    1984 Volume 37 Issue 5 Pages 487-493
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Formation of the basic antibiotic, K-582 was stimulated by supplying Metarrhizium anisopliae U-47 with several amino acids present in its structure. The addition of L-arginine to the basal medium resulted in the almost exclusive formation of K-582 B, while L-lysine increased K-582 A formation. Some carbon sources were observed to have effects similar to those obtained with the above mentioned amino acids. Furthermore, when L-arginine was added in excess to the basal medium, free γ-hydroxyarginine, which is a major constituent of the antibiotic, accumulated extra- and intra-cellularly. Free γ-hydroxyarginine isolated from the culture broth of this microorganism was the threo-L-isomer. K-582 formation was repressed by glycerol, which exerted catabolite repression of γ-hydroxyarginine synthesis.
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  • SATOSHI OMURA, YOSHITAKE TANAKA, HIROSHI MAMADA, ROKURO MASUMA
    1984 Volume 37 Issue 5 Pages 494-502
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The production of tylosin by Streptomyces fradiae KA-427 in a defined medium was inhibited by ammonium ions and by inorganic phosphate. The production of protylonolide, an early lactonic intermediate of tylosin biosynthesis with the same carbon skeleton as tylosin aglycone, by a mutant of strain KA-427 was also reduced by these two kinds of ions. In contrast, the bioconversion of protylonolide to tylosin by another mutant was less susceptible to ammonium ions but was sensitive to inorganic phosphate. The addition of protylonolide to a culture of S. fradiae KA-427 increased the tylosin yield, suggesting that aglycone synthesis is limiting under the conditions used. When L-valine, L-leucine, L-isoleucine, L-threonine, or the corresponding 2-keto acid was added to the culture medium, the protylonolide titer increased. The addition of [14C]valine gave rise to [14C]protylonolide. 13C NMR spectroscopic analysis revealed that iso-butyrate, which is a valine metabolite, was incorporated into protylonolide at the carbons known to originate from propionate and n-butyrate. Taking account of these findings, the regulation of tylosin biosynthesis in S. fradiae by ammonium ion is discussed in relation to amino acid metabolism.
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  • Y.-Q. SHEN, J. HEIM, N. A. SOLOMON, S. WOLFE, A. L. DEMAIN
    1984 Volume 37 Issue 5 Pages 503-511
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A variety of inorganic and organic nitrogen sources were added to fermentation media to determine their regulatory effects on the production of β-lactam antibiotics by Cephalosporium acremonium. (NH4)2SO4 at concentrations higher than 100 mm (1.3%) strongly inhibited β-lactam production. L-Asparagine and L-arginine proved to be the best nitrogen sources tested for β-lactam production. The optimum concentration of asparagine was 1.2%. Higher concentrations led to NH3 accumulation, increase in pH, and lower growth rates. Addition of tribasic magnesium phosphate [Mg3(PO4)2•8H2O] to the (NH4)2SO4-containing medium stimulated β-lactam production markedly and ammonium repression of the ring-expansion enzyme was reversed. It appears that the ring-expansion step is a very sensitive part of β-lactam biosynthesis in C. acremonium with respect to nitrogen source repression. Other enzymes may also be sensitive in view of the fact that nitrogen source derepression not only led to increases in cephalosporin C but, to a lesser extent, penicillin N and total β-lactam titers.
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  • YUTAKA SHINDOH, MICHIKO M. NAKANO, HIROSHI OGAWARA
    1984 Volume 37 Issue 5 Pages 512-517
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A series of high copy number plasmids designated pSRC were isolated from Streptomyces roseochromogenus S264. The pSRC series were found to be self-transmissible by conjugation and to elicit lethal zygosis (Ltz). Using the Ltz phenotype to detect plasmid transformants, the pSRC plasmids were shown to have a wide host range. Among them pSRCl consisted of two different plasmids with the same molecular weight, Psrc1a and 1b. Information regarding restriction sites suitable for the insertion of DNA was obtained by cloning the thiostrepton resistance gene from pIJ702 into pSRC1b. The single Bgl II site of pSRC1b was nonessential for replication and pock-formation. The pSRC plasmids may be suitable as cloning vectors in Streptomyces.
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  • SHOKICHI OHUCHI, AKIRA OKUYAMA, HIROSHI NAGANAWA, TAKAAKI AOYAGI, HAMA ...
    1984 Volume 37 Issue 5 Pages 518-521
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The biosynthetic pathways of arphamenines A and B were studied. Arphamenine A was derived from acetic acid, L-arginine and L-phenylalanine, and arphamenine B from acetic acid, L-arginine and L-tyrosine.
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  • A. SCHEIDEGGER, M. T. KÜENZI, J. NÜESCH
    1984 Volume 37 Issue 5 Pages 522-531
    Published: 1984
    Released: April 19, 2006
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    The catalytic properties of the partially purified deacetoxycephalosporin C (DAOC)-synthetase and DAOC-hydroxylase from an industrial strain of Cephalosporium acremonium were studied. After mechanical breakage of the cells, purification was achieved by fractional (NH4) 2SO4 precipitation, gel chromatography on Sephadex G-75, ion exchange chromatography on DEAE-Trisacryl M and two isoelectric focusing steps. The two enzyme activities could not be separated. Indirect evidence was obtained from SDS-polyacrylamide gel electrophoresis of the purest fractions obtained by isoelectric focusing that the two reactions are catalyzed by a single enzyme with a molecular weight of 33, 000±2, 000 and a pI of 4.6±0.1. Both reactions require α-ketoglutarate, FeSO4, ascorbate and O2, whereas additional ATP shows only a slight stimulation.
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  • JIRO GOTO, KAZUO SAKANE, YOSHIHARU NAKAI, TSUTOMUT ERAJI, TAKASHI KAMI ...
    1984 Volume 37 Issue 5 Pages 532-545
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The synthesis and in vitro activity of 7β-(2-aminopyridyl-2-alkoxyiminoacetamido)cephalosporins with various substituents at the 3-position are described. The effects of substitution pattern on the pyridine ring, oxime substituent and 3-substituent were studied as a function of the MIC values. Of these various kinds of derivatives, 7β-[2-(2-aminopyridin-6-yl)-2-alkoxy-iminoacetamido]cephatosporins exhibited significantly higher activity against most of microorganisms.
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  • JIRO GOTO, KAZUO SAKANE, YOSHIHARU NAKAI, TSUTOMU TERAJI, TAKASHKI AMI ...
    1984 Volume 37 Issue 5 Pages 546-556
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The synthesis and the antibacterial activity of 7β-[2-(aminopyrimidinyl)-2-oxyiminoacetamido] cephalosporins with various substituents at the 3-position in the cephem nucleus are described. The 7β-[2-(4-aminopyrimidin-2-yl)-2-methoxyiminoacetamido]cephalosporin derivative (1) showed significantly higher activity than the corresponding 2-aminopyrimidin-4-yl derivative (2) against Gram-negative bacteria. It was also higher in potency against Escherichia coli and Serratia marcescens than the aminopyridyl compound (4).
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  • JIRO GOTO, KAZUO SAKANE, TSUTOMU TERAJI
    1984 Volume 37 Issue 5 Pages 557-571
    Published: 1984
    Released: April 19, 2006
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    The synthesis and in vitro antibacterial activity of 7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2-oxyiminoacetamido]cephalosporins with various substituents at the 3-position in the cephem nucleus are described. Aminothiadiazolyl cephalosporins having pyridiniomethyl groups at the 3-position exhibited excellent activity against all organisms, particularly against Pseudomonas aeruginosa.
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  • JAMES B. RAKE, DAVID J. NEWMAN, PAUL ACTOR
    1984 Volume 37 Issue 5 Pages 572-576
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The binding of cefonicid (SK&F 75073), a new parenteral cephalosporin, to the penicillinbinding proteins (PBPs) of Escherichia coil K-12 (strain KN-126) was determined by competitive binding studies versus benzyl[14C]penicillin. Cefonicid showed its greatest affinity for PBPs 1a>3>1b, bound with low affinity to PBPs 4>2, and did not bind to PBPs 5 and 6. Provisional affinity constants (cefonicid concentration that gave 50% inhibition of [14C]penicillin binding) were determined: PBP 1a, <0.25μg/ml; PBP 3, 0.7μg/ml; PBP 1b, 10μg/ml; PBP 4, 26μg/ml; PBP 2, 90μg/ml; PBPs 5 and 6 >256μg/ml. Direct binding studies with [14C]-cefonicid confirmed this pattern of binding. Subinhibitory concentrations of cefonicid (MIC, broth 0.2μg/ml, agar 0.4μg/ml) induced filamentation of E. coil KN-126. This implies that PBP 3 is the primary inhibitory site despite the higher affinity of PBP 1a for this cephalosporin.
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  • SHINZABUROU MINAMI, NOBUYUKI MATSUBARA, AKIRA YOTSUJI, HARUMI ARAKI, Y ...
    1984 Volume 37 Issue 5 Pages 577-587
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The enzymic inactivation of cephamycins, i.e. cefoxitin, cefmetazole, cefotetan and cefbuperazone, was investigated by means of bioassay, high pressure liquid chromatography (HPLC) and spectrophotometric analysis using three types of cephalosporinase (CSase, RICHMOND type Ia, Ib and Ic) and one penicillinase (PCase, TEM type). These four cephamycins were not inactivated by Ic CSase and TEM type PCase or producers of these enzymes. However, the inactivation of cefmetazole and cefoxitin was noted when they were incubated in the cultures of CSase (Ia and Ib)-producers or incubated with a large amount of these purified enzymes although the inactivation of cefbuperazone was not noted. HPLC of culture fluid or enzyme solution which contained cefmetazole or cefoxitin and were incubated at 37°C showed that metabolites of cefmetazole or cefoxitin appeared as the drug disappeared. In addition, the appearance of metabolites corresponded to the loss of the drug's bioactivities and the absorption of iodine. UV and IR spectra of cefmetazole which were taken after incubation with the purified CSase showed the cleavage of the β-lactam ring.
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  • DAVINDER S. PLAHA, HENRY J. ROGERS, GARY W. WILLIAMS
    1984 Volume 37 Issue 5 Pages 588-595
    Published: 1984
    Released: April 19, 2006
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    The scandium complex of enterochelin is known to be assimilated and degraded by enterobacterial pathogens, liberating intracellular scandium. Macromolecular synthesis was inhibited in the order RNA, protein, DNA and phospholipid. Some component of heat-inactivated serum acts in concert with the complex inducing RNA degradation and killing. Both processes are inhibited by dinitrophenol. These biochemical changes resemble those found during complement mediated killing. An examination of the effect on synchronously growing cells suggests that the complex may exert its primary effect during the initiation of chromosome replication.
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  • KEITA MATSUNAGA, TOSHIO NISHIMURA, NOBUO TANAKA
    1984 Volume 37 Issue 5 Pages 596-601
    Published: 1984
    Released: April 19, 2006
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    Cellular uptake of habekacin, 1-N(4-amino-2-hydroxybutyryl)dibekacin, was studied by incubating exponentially growing culture of Escherichia coli Q13 and its kanamycin-resistant mutants with [3H]habekacin. Kanamycin-resistant mutants, in which the resistance is due to alteration of ribosomes, were cross-resistant to habekacin, and showed a lower uptake of [3H]habekacin than the parental cells, suggesting that binding to ribosomes accelerates cellular uptake of habekacin. Cellular accumulation of [3H]habekacin by wild type cells was markedly inhibited by low temperature and by 2, 4-dinitrophenol, suggesting that uptake of habekacin involves energy-dependent transport. The uptake of [3H]habekacin was reduced by various aminoglycoside antibiotics, suggesting common transport systems and/or common internal binding sites on the ribosome. Intracellular accumulation of [3H]dibekacin was reduced by habekacin, suggesting that both antibiotics possess a common transport system and/or common binding sites on the ribosome. Dibekacin was a better competitor than amikacin, suggesting that the dibekacin moiety of habekacin molecule, but not the 4-amino-2-hydroxybutyryl moiety, participates in the transport and/or binding to the ribosome. Binding of [3H]habekacin to E. coli ribosomes was reversed by various aminoglycosides and the degree of inhibition paralleled the one of cellular uptake, suggesting that competition by aminoglycosides for the habekacin uptake occurs at the ribosomal level.
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  • HIDEO SUZUKI, YOSHIKAZU SUGIMOTO, KUMIKO TANAKA, TOSHIO NISHIMURA, NOB ...
    1984 Volume 37 Issue 5 Pages 602-609
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A macromomycin (MCR)-resistant subline of mouse lymphoblastoma L5178Y cells was isolated after successive treatment of tumor-bearing mice with the antibiotic for 7 transplant generations, followed by cloning in culture in MCR-containing soft agar medium. The resistant cell line was about 17 times more resistant to MCR than was the parental cell line and exhibited cross-resistance to neocarzinostatin, mitomycin C and adriamycin in a similar degree to MCR. No significant cross-resistance was observed with aclarubicin, bleomycin and neothramycin. Alkaline phosphodiesterase activity in the plasma membrane of resistant cells was higher than that of parental cells. Uptake and efflux studies with [3H]adriamycin suggested that the resistance is due to decreased uptake and increased efflux of the antibiotic in resistant cells. Hybridization studies with MCR-sensitive and -resistant cells showed that the MCR resistance is a codominant trait in somatic cell hybrids.
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  • HARUO SETO, ICHIKO TAJIMA, HIROKO AKAO, KAZUO FURIHATA, NOBORU OTAKE
    1984 Volume 37 Issue 5 Pages 610-613
    Published: 1984
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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