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I. TAXONOMY OF THE PRODUCING STREPTOMYCETE AND ISOLATION OF THE ACTIVE PRINCIPLE
CLAUDE VÉZINA, ALICIA KUDELSKI, S. N. SEHGAL
1975 Volume 28 Issue 10 Pages
721-726
Published: 1975
Released on J-STAGE: April 12, 2006
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A streptomycete was isolated from an Easter Island soil sample and found to inhibit
Candida albicans, Microsporum gypseum and
Trichophyton granulosum. The antibioticproducing microorganism was characterized and identified as
Streptomyces hygroscopicus. The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin. Rapamycin is mainly active against
Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 μg/ml. Its apparent activity against
Microsporum gypseum and
Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi. No activity was observed against gram-positive and gram-negative bacteria. Acute toxicity in mice is low.
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II. FERMENTATION, ISOLATION AND CHARACTERIZATION
S. N. SEHGAL, H. BAKER, Claude VÉZINA
1975 Volume 28 Issue 10 Pages
727-732
Published: 1975
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Rapamycin is a new antifungal antibiotic produced by
Streptomyces hygroscopicus NRRL 5491. It was isolated from the mycelium by solvent extraction, purified by silica gel column chromatography and crystallized as a colorless solid which melts at 183-185°C and has the empirical formula C
56H
89NO
14. From its characteristic ultraviolet absorption spectrum rapamycin can be classified as a triene. It is highly active against various
Candida species, especially
Candida albicans. Its activity is compared with that of amphotericin B, candicidin and nystatin.
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A. D. ARGOUDELIS, S. A. MIZSAK, L. BACZYNSKYJ
1975 Volume 28 Issue 10 Pages
733-736
Published: 1975
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A new metabolite N-acetyl-L-phenylalanyl-L-phenylalaninol was isolated from culture filtrates of
Emericellopsis salmosynnemata which produces zervamicins I and II. The structure was assigned from spectral properties and degradative studies.
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TOMIO TAKEUCHI, HIDEO CHIMURA, MASA HAMADA, HAMAO UMEZAWA
1975 Volume 28 Issue 10 Pages
737-742
Published: 1975
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Many streptomyces strains produced an inhibitor of crude glyoxalase prepared from rat liver which did not inhibit glyoxalase I prepared from yeast. Another inhibitor, C
11H
14O
6, which inhibited glyoxalases prepared from both rat liver and yeast was obtained from a cultured broth of
Streptomyces griseosporeus and crystallized. Preincubation of this inhibitor with reduced glutathione increased its inhibitory activity, which suggested its reaction with reduced glutathione. It showed a strong inhibition of growth of HeLa cells and inhibition of EHRLICH ascites carcinoma by daily injection. It also showed weak inhibition of the solid type of EHRLICH carcinoma and prolonged the survival period of mice inoculated with L-1210 cells.
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HIDEO CHIMURA, HIKARU NAKAMURA, TOMOHISA TAKITA, TOMIO TAKEUCHI, HAMAO ...
1975 Volume 28 Issue 10 Pages
743-748
Published: 1975
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The structure of a glyoxalase I inhibitor (
I), isolated from a cultured broth of
Streptomyces griseosporeus, was found to be 2-crotonyloxymethyl-4, 5, 6-trihydroxy-cyclohex-2-enone by chemical studies. Stereochemistry and absolute configuration were determined to be 4R, 5R and 6R by X-ray crystallographic analysis of a bromine-containing crystalline derivative. The crotonyloxy group of
I shows a surprising proclivity to be displaced by SH-compounds. This property is shown to be the basis for its biological activity.
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TAKUO SAKAI, D. PERLMAN
1975 Volume 28 Issue 10 Pages
749-756
Published: 1975
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Two extracellular antibiotics produced by
Mycoplasma sp. RP III growing in serum-containing media have been purified by solvent extraction and ion-exchange chromatography. Factor I inhibits Gram-positive and Gram-negative bacteria
in vitro and a crude preparation protected mice from
Pseudomonas and
Staphylococcus infections; it is of low cytotoxicity. Factor II, a lipid, inhibits Gram-positive and Gram-negative bacteria,
Candida species, and is as cytotoxic as the actinomycins.
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MITSUHIRO NUMATA, KAZUO NITTA, RYOZO UTAHARA, KENJI MAEDA, HAMAO UMEZA ...
1975 Volume 28 Issue 10 Pages
757-763
Published: 1975
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Revistin, a substance that strongly inhibits the reverse transcriptase activity of murine leukemia virus in our screening system, was obtained from a cultured broth of a soil streptomyces which was closely related to
Streptomyces filipinensis. The assay method for the activity was based on the inhibition by a test material of the incorporation of
3H-dTMP into DNA synthesized by the reverse transcriptase of an oncogenic RNA virus. Crude revistin was isolated by serial procedures of salting out with ammonium sulfate and precipitation with cetylpyridinium chloride. The crude material showed neither antibacterial nor antifungal activity. It exhibited inhibition against splenomegaly in mice caused by RAUSCHER leukemia virus infection.
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STUDIES ON ANTIBIOTICS FROM THE GENUS BACILLUS. VII
JUN'ICHI SHOJI, TOSHIYUKI KATO
1975 Volume 28 Issue 10 Pages
764-769
Published: 1975
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N-Bromosuccinimide cleavage reaction on cerexin A liberated
allo-isoleucine. Treatment with conc. hydrochloric acid cleaved the antibiotic into two peptide fragments selectively at a γ-hydroxylysine residue. Deacylation with an enzyme preparation from
Pseudomonas sp. afforded deacyl cerexin A. The amino acid sequences of these peptide fragments were examined by EDMAN degradation. From all the results, the entire amino acid sequence of cerexin A was deduced.
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SELECTION OF AND COSYNTHESIS BY NON-PLATENOMYCIN-PRODUCING MUTANTS
TAMOTSU FURUMAI, MAKOTO SUZUKI
1975 Volume 28 Issue 10 Pages
770-774
Published: 1975
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In a search for blocked mutants which may produce a biosynthetic intermediate, mutation by N-methyl-N'-nitro-N-nitrosoguanidine treatment and/or ultra-violet irradiation were performed on platenomycin-producing
Streptomyces platensis subsp.
malvinus MCRL 0388 (NRRL 3761). Twenty four non-platenomycin-producing stable mutants were thus obtained and tested for cosynthesis ability. Antibiotic cosynthesis with a pair of these mutants made it possible to detect the producer of an intermediate. Among these mutants which were classified into eight groups (A to G and doubtful groups), mutants of groups A and B appeared from their complementation pattern to be the useful producers of biosynthetic intermediates of platenomycin.
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PRODUCTION, ISOLATION AND STRUCTURES OF 3-O-PROPIONYL-5-OMYCAMINOSYL PLATENOLIDES I AND II, 9-DEHYDRO DEMYCAROSYL PLATENOMYCIN AND DEMYCAROSYL PLATENOMYCIN
TAMOTSU FURUMAI, MAKOTO SUZUKI
1975 Volume 28 Issue 10 Pages
775-782
Published: 1975
Released on J-STAGE: April 12, 2006
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Four basic glycosides have been isolated from the fermentation broth of the blocked mutants of
Streptomyces platensis subsp. malvinus MCRL 0388. These compounds isolated and purified by solvent extraction and column chromatography were identified as 3-O-propionyl-5-O-mycaminosyl platenolides I (PPL-I-MC) and II (PPL-II-MC), 9-dehydro demycarosyl platenomycin (DDM-PLM) and demycarosyl platenomycin (DM-PLM).
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PRODUCTION, ISOLATION AND STRUCTURES OF PLATENOLIDES I AND II
TAMOTSU FURUMAI, MAKOTO SUZUKI
1975 Volume 28 Issue 10 Pages
783-788
Published: 1975
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Two neutral macrocyclic lactones designated platenolides I and II have been isolated as the major products from the fermentation broth of the blocked mutants of
Streptomyces platensis subsp.
malvinus. These two compounds were isolated by solvent extraction and purified by column chromatography. Both platenolides [PL-I: C
20H
32O
6, PL-II: C
20H
34O
6] are closely related to the platenomycin aglycone.
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BIOSYNTHESIS OF PLATENOMYCINS
TAMOTSU FURUMAI, KATSUO TAKEDA, MAKOTO SUZUKI
1975 Volume 28 Issue 10 Pages
789-797
Published: 1975
Released on J-STAGE: April 12, 2006
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To elucidate the biosynthetic pathway of platenomycin (PLM), biosynthetic relationships of platenolides I (PL-1) and II (PL-II), 3-O-propionyl-5-O-mycaminosyl platenolides I (PPL-I-MC) and II (PPL-II-MC), 9-dehydro demycarosyl platenomycin (DDM-PLM), demycarosyl platenomycin (DM-PLM) and 4"-deacyl platenomycin (DA-PLM) were examined with growing cultures or the washed mycelium of blocked mutants of
Streptomyces platensis subsp.
malvinus MCRL 0388, a platenomycin-producing organism. As a result, it was revealed that PLM was biosynthesized from PL-I
via DM-PLM and DAPLM along the pathways shown in Chart 1. 4"-Isovaleroyl unit of PLM-A
1 and 4"-propionyl unit of PLM-B
1 were respectively derived from L-leucine and L-isoleucine.
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KENGO SAKAGUCHI, MASATOSHI TSUJINO, KIMIO MIZUNO, KAZUO HAYANO, NAKAO ...
1975 Volume 28 Issue 10 Pages
798-803
Published: 1975
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The aglycone of the nucleoside antibiotic, bredinin, was as strongly cytotoxic to L5178Y cells as bredinin. The cytotoxic properties of the aglycone were very similar to those of bredinin and the minimum inhibitory concentrations of both were 10
-5M. The growth inhibitory effects of both agents regardless of their concentrations, were reversed by guanylic acid, guanosine or guanine. However, on increasing the concentrations of these agents, the reversing effect of guanylic acid decreased gradually, the dose-response curves for the two agents being similar. Both agents inhibited the incorporation of thymidine and uridine, but not leucine into macromolecules in L5178Y cells and their inhibitory effects were reversed to similar extents by guanylic acid.
On the other hand, the growth inhibitory effect of the aglycone on L5178Y cells was prevented by adenine only, though not by adenosine or adenylic acid while the effect of bredinin was not prevented by adenine. These results suggest that the aglycone itself does not inhibit growth, but that its effect is due to its conversion to bredinin by an enzyme such as adenine phosphoribosyl transferase. For recovery of growth, three moles of adenine were required per mole of the aglycone. When the aglycone was administered orally to rats, bredinin was recovered in their serum and urine.
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TOYOJI OKUBO, MATSUHISA INOUE, SUSUMU MITSUHASHI
1975 Volume 28 Issue 10 Pages
804-808
Published: 1975
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The antibacterial activity of cephalosporin (CS) and semisynthetic penicillins was studied using CS-resistant strains of Escherichia freundii and
Proteus morganii. A synergistic growth inhibitory action toward these microorganisms was demonstrated by a qualitative method and confirmed by a quantitative determination.
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HERBERT I. HADLER, JOHN M. DEMETRIOU
1975 Volume 28 Issue 10 Pages
809-818
Published: 1975
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Currently N-acetoxy-N-acetyl-2-aminofluorene is favored by many investigators to be a model of the ultimate electrophilic carcinogenic agent derived metabolically from the carcinogen N-acetyl-2-aminofluorene. The model induced
in vitro a delayed ATP energized increase in mitochondrial volume as indicated by the decrease in absorbancy at 520 nm. The ATP energized decrease in absorbancy was inhibited by rutamycin, 2, 4-dinitrophenol and a high level of antimycin known to induce ATPase activity. The ATP energized effect was not altered either by rotenone or by a low level of antimycin known to inhibit respiration without inducing ATPase activity. Malate or potassium ion did not affect the phenomenon, however, sulfate ion which has been implicated in liver carcinogenesis shortened the induction period. Showdomycin stimulated the phenomenon. N-Acetoxy-N-acetyl-2-aminofluorene interacts with the machinery of oxidative phosphorylation. N-Acetoxy-N-acetyl-2-aminofluorene was enzymically converted by the mitochondria to N-hydroxy-N-acetyl-2-aminofluorene. These findings extend the experimental confluence of oxidative phosphorylation with carcinogenesis.
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RUIKO OIWA, M ICHIKO KATAGIRI, NAOHISA TANAKA, YOKO TAKAHASHI, KEIKI S ...
1975 Volume 28 Issue 10 Pages
819-820
Published: 1975
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TADAYUKI ISHIYAMA, TAKAKI FURUTA, MAKOTO TAKAI, YOICHIRO OKIMOTO
1975 Volume 28 Issue 10 Pages
821-823
Published: 1975
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JUICHI AWAYA, TADATAKA KESADO, SATOSHI OMURA, GABOR LUKACS
1975 Volume 28 Issue 10 Pages
824-827
Published: 1975
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HIROSHI NAGANAWA, NOBUKO USUI, TOMOHISA TAKITA, MASA HAMADA, HAMAO UME ...
1975 Volume 28 Issue 10 Pages
828-829
Published: 1975
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TOSHIKAZU OKI, YASUE MATSUZAWA, AKIHIRO YOSHIMOTO, KENJI NUMATA, IWAO ...
1975 Volume 28 Issue 10 Pages
830-834
Published: 1975
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STEPHEN HANESSIAN, TETSUYOSHI TAKAMOTO, ROBERT MASSE
1975 Volume 28 Issue 10 Pages
835-837
Published: 1975
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P. F. WILEY, V. P. MARSHALL
1975 Volume 28 Issue 10 Pages
838-840
Published: 1975
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ULFERT HORNEMANN, JAMES H. EGGERT
1975 Volume 28 Issue 10 Pages
841-843
Published: 1975
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