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KEITA KONO, MASAHIRO TANAKA, TADAYOSHI MIZUNO, KENTARO KODAMA, TAKESHI ...
2000 Volume 53 Issue 8 Pages
753-758
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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In the course of our screening for inhibitors of sphingosine kinase, we found a series of active compounds in a culture broth of a novel marine bacterium, SANK 71896. The structures of the compounds, named B-5354a, b and c, were elucidated by a combination of spectroscopic analyses to be new esters of 4-amino-3-hydroxybenzoic acid with long-chain unsaturated alcohols. B-5354a, b and c inhibit sphingosine kinase activity with IC
50 values of 21, 58 and 38 μM, respectively.
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KEITA KONO, MASAHIRO TANAKA, TAKESHI OGITA, TAKAFUMI KOHAMA
2000 Volume 53 Issue 8 Pages
759-764
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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B-5354c is a new inhibitor of sphingosine kinase from a novel marine bacterium, SANK 71896. Kinetic study revealed that B-5354c inhibits sphingosine kinase with a
Ki value of 12μM. The inhibition is noncompetitive with respect to sphingosine. The compound also inhibits sphingosine-1-phosphate formation in human platelets. Experiments using synthetic derivatives of B-5354c indicate that all the three functional groups,
i.e., the long unsaturated aliphatic chain, 4-amino and 3-hydroxyl groups are necessary to inhibit sphingosine kinase.
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Taxonomy, Fermentation, Isolation and Biological Activities In Vitro and In Vivo
TAKAFUMI ISHII, KOZO HAYASHI, TSUNEAKI HIDA, YASUHARU YAMAMOTO, YUKIMA ...
2000 Volume 53 Issue 8 Pages
765-778
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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A novel Ras-farnesyltransferase inhibitor designated TAN-1813 was isolated from the culture broth of a fungus strain, FL-41510, isolated as a plant endophyte. The producer was taxonomically characterized as
Phoma sp. FL-41510. TAN-1813 inhibited rat brain farnesyltransferase and geranylgeranyltransferase I activity with IC
50 values of 23 μg/ml and 47 μg/ml, respectively. TAN-1813 showed mixed-type inhibition with respect to farnesylpyrophosphate and noncompetitive inhibition with respect to a K-Ras C-terminal pep tide. It also inhibited the
in situ farnesylation of cellular Ras proteins in a K-ras transformant (NIH3T3/K-ras) of mouse embryonic fibroblast cell line NIH3T3.
TAN-1813 inhibited the proliferation of various human cancer cells, some of which harbor activated ras alleles, with IC
50 values of 15-110ng/ml as well as that of NIH3T3 and NIH3T3/K-ras cells with IC
50s of 540 and 310ng/ml, respectively. Flow cytometric analysis indicated that TAN-1813 arrests NIH3T3/K-ras cells at both Gl and G2/M phases of the cell cycle. In addition, TAN-1813 was found to induce morphological reversion of NIH3T3/K-ras cells from the transformed phenotype. Antitumor activity of TAN-1813 against human fibrosarcoma HT-1080 and NIH3T3/K-ras tumors in nude mice was also verified.
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I. Taxonomy, Fermentation, Isolation and Biological Activities
JUDITH SCHIMANA, HANS-PETER FIEDLER, INGRID GROTH, RODERICK SUBMUTH, W ...
2000 Volume 53 Issue 8 Pages
779-787
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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Two novel angucyclinone-type antibiotics, simocyclinones D4 and D8, were detected in the mycelium extract of
Streptomyces antibioticus Tü 6040 by HFLC-diode-array and HPLCelectrospray-mass-spectrometry screening. The compounds show antibiotic activities against Gram-positive bacteria and cytostatic effects on various tumor cell lines.
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I. Production, Isolation and Biological Activities
YUHTA MASUOKA, KAZUO SHIN-YA, YONG-BAE KIM, MINORU YOSHIDA, KOJI NAGAI ...
2000 Volume 53 Issue 8 Pages
788-792
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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A new metabolite, diheteropeptin, was found in the culture broth of
Diheterospora chlamydosporia Q58044 by screening for TGF-β-like active substances. Diheteropeptin was extracted from the culture supernatant and purified by a series of chromatographies such as silica gel, gel filtration and HPLC. Diheteropeptin exhibited cytostatic activity in MvlLu cells with an IC
50 value of 20.3 μM and inhibited histone deacetylase.
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II. Physico-chemical Properties and Structure Elucidation
YUHTA MASUOKA, KAZUO SHIN-YA, KAZUO FIMIHATA, HISAO MATSUMO, YUKIHIRO ...
2000 Volume 53 Issue 8 Pages
793-798
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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The structure of diheteropeptin (
1), a TGF-β-like active substance from
Diheterospora chlamydosporia Q58044, was determined to be a new cyclotetrapeptide,
cyclo[2-aminoisobutyryl-(
S)-phenylalanyl-(
R)-prolyl-(2
S, 8
R, 9
R)-2-amino-8, 9-dihydroxydecanoyl-] by NMR, mass spectrometric and chemical studies.
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JU-YOUNG KWON, HA-WON JEONG, HYAE-KYEONG KIM, KUI-HYUN KANG, YIE-HWA C ...
2000 Volume 53 Issue 8 Pages
799-806
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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Selective inhibition against the yeast MetAP2 (methionine aminopeptidase type 2) was detected in the fermentation broth of a fungus F2757 that was later identified as
Penicillium janczewskii. A new compound
cis-fumagillin methyl ester (
1) was isolated from the diazomethane treated fermentation extracts together with the known compound fumagillin methyl ester (
2). The
cis-fumagillin methyl ester, a stereoisomer of fumagillin methyl ester at the C2'-C3' position of the aliphatic side chain, selectively inhibited growth of the
map1 mutant yeast strain (MetAPI deletion strain) at a concentration as low as 1 ng. However, the wild type yeast
w303 and the mutant
map2 (MetAP2 deleted) strains were resistant up to 10 μg of the compound. In enzyme experiments, compound
1 inhibited the MetAP2 with an IC
50 value of 6.3nM, but it did not inhibit the MetAPl (IC
50 >200μ, M). Compound
2 also inhibited the MetAP2 with an IC
50 value of 9.2nM and 105 μM against MetAPl.
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I. Taxonomic Studies of the Producing Microorganism and Fermentation
W. ARETZ, J. MEIWES, G. SEIBERT, G. VOBIS, J. WINK
2000 Volume 53 Issue 8 Pages
807-815
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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A strain that produces new lipopeptide antibiotics is a new species of the genus
Actinoplanes for which we propose the name
Actinoplanes friuliensis (type strain: HAG 010964). The strain is an actinoplanete actinomycete having cell wall II composition and forming sporangia. Comparisons with
Actinoplanes spp. which have similarities with our isolate, including fatty acid analysis, showed that the isolate belongs to a new species. Taxonomic studies and fermentation are presented.
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II. Isolation and Structural Characterization
LÁSZLÓ VÉRTESY, EBERHARD EHLERS, HERBERT KOGLER, ...
2000 Volume 53 Issue 8 Pages
816-827
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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Four novel lipopeptide antibiotics, friulimicins A, B, C, and D, were isolated from cultures of
Actinoplanes friuliensis HAG 010964 after fermentation in different nutrient media. The new compounds were separated by ion-exchange chromatography from the acidic lipopeptides of the amphomycin type also present in the culture fluid, compounds A-1437 A, B, E, and G. The principal constituent friulimicin B, C
59H
94N
14O
19, was structurally characterized by mass spectrometric investigations of its hydrolysis and partial degradation products and by sequencing of the cyclic acyl peptide. The NMR data of friulimycin B and the amphomycin constituent A-1437 B were completely assigned by a variety of 2-D experiments, and confirmed the structures determined by mass spectrometry. All 8 lipopeptides possess an identical peptide macrocycle as their central element, linked
via a diaminobutyric acid
N-terminal either to an acylated asparagine residue or, in the case of the amphomycin series, to an acylated aspartic acid residue. The structures of the amphomycins have now been revised to take account of the peptide framework described herein and the determined
cis-configuration of the exocyclic double bond. As a consequence of their higher isoelectric points, the new compounds friulimicin A, B, C, and D have different properties than the amphomycins.
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YUJI MIYAMOTO, SHINJI OHTA, OSAMU JOHDO, YASUNORI NAGAMATSU, AKIHIRO Y ...
2000 Volume 53 Issue 8 Pages
828-836
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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A new hybrid anthracycline antibiotic was produced by heterologous expression of
dnrK encoding carminomycin 4-
O-metyltransferase in an epelmycin-producing
Streptomyces violaceus. pMK100 was constructed by insertion of
Steptomyces peucetius dnrK gene in
Steptomyces-expresion vector pIJ6021 and introduced to the epelmycin producer. The transformant produced a hybrid anthracycline antibiotic together with host epelmycins when cultured in antibiotic production medium in the presence of thiostrepton. The hybrid anthracycline was determined to be 7-
O-L-rhodosaminyl-4-
O-methyl-ε-rhodomycinone (4-
O-memylepelmycin D). However, the attempts on production of hybrid 4-
O-methyl aclarubicin and 4-
O-methyl-1-deoxyobelmycin by the transformants of aclarubicin and 1-deoxyobelmycin producers with pMK100 were unsuccessful.
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M. S. PUAR, E. BARRABEE, M. HALLADE, M. PATEL
2000 Volume 53 Issue 8 Pages
837-838
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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H. DÖRFELT, B. SCHLEGEL, U. GRÄFE
2000 Volume 53 Issue 8 Pages
839-843
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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MASATOSHI TANIGUCHI, MASATO WATANABE, KOJI NAGAI, KEN-ICHI SUZUMURA, K ...
2000 Volume 53 Issue 8 Pages
844-847
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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TAIJIRO TOMIKAWA, KAZUO SHIN-YA, KEIKO FURIHATA, TAISEI KINOSHITA, ATS ...
2000 Volume 53 Issue 8 Pages
848-850
Published: August 25, 2000
Released on J-STAGE: September 19, 2008
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