Haematocin, a new antifungal diketopiperazine produced by Nectria haematococca Berk. et Br. (880701a-1) causing nectria blight disease on ornamental plants.

A new antifungal diketopiperazine named haematocin was isolated from the culture broth of Nectria haematococca Berk. et Br. (880701a-1) causing blight disease on ornamental plants, Phalaenopsis spp. and Doritanopsis spp. Its structure was established by spectroscopic methods. Haematocin inhibited the germ-tube elongation and spore-germination of Pyricularia oryzae at the ED50 values of 30 microg/ml and 160 microg/ml, respectively.

New types of liposidomycins produced by Streptomyces that inhibit bacterial peptidoglycan synthesis. Structure elucidation of fatty acid components by tandem mass spectrometry.

The structures of the fatty acid components of various new liposidomycins were determined using tandem mass spectrometry; the negative FAB/MS/MS/MS technique for liposidomycins with a 3-methylglutaric acid moiety and the negative FAB/MS/MS technique for liposidomycins without a 3-methylglutaric acid moiey. This structural information was obtained by analysis of peaks due to charge-remote fragmentations for 3-hydroxycarboxylate anions or carboxylate anions which were generated from liposidomycin molecules in a mass spectrometer. The MS/MS/MS technique that can exclude the matrix-derived and/or interfering ions showed higher sensitivity than the MS/MS technique.

Signal transduction inhibitors, hibarimicins, A, B, C, D and G produced by Microbispora. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties.

Strain TP-AO121 which produces a complex of novel tyrosine kinase inhibitors designated hibarimicins A, B, C, D and G was considered to be a new subspecies of Microbispora rosea, and the name, Microbispora rosea subsp. hibaria, was proposed. Hibarimicins A, B, C and D specifically inhibited the src tyrosine kinase activity without affecting protein kinase A or protein kinase C. They also showed in vitro anti-Gram-positive bacterial and antitumor activities. The molecular formulae of hibarimicins A, B, C, D and G were assigned to be C85H112O37, C85H112O37, C83H110O36, C85H112O38, and C85H112O39 respectively.

S19159, a modulator of neurite outgrowth produced by the ascomycete Preussia aemulans. I. Producing strain, fermentation, isolation and biological activity.

A modulator of neurite outgrowth, designated S19159, was isolated from the fermentation broth of fungal strain 19159. This fungus was identified as the loculoascomycete, Preussia aemulans (Rehm) von Arx. In the presence of S19159, the number of neurites extending from the cell bodies of cerebral cortical neurons was markedly reduced. The effect of S19159 was observed specifically in neurons from the central nervous system. The compound exhibited similar activities on cultured cortical, hippocampal and cerebeller neurons but was without detectable effect on dorsal root ganglion neurons and PC12 cells.

Novel amino acid metabolite produced by Streptomyces sp.: I. Taxonomy, isolation, and structural elucidation.

A strain of streptomycete isolated from a soil sample was found to produce a novel amino acid metabolite. The compound was purified from the culture fluid by chromatography, using cation exchange resin, a synthetic adsorbent, and finally by preparative HPLC with a reverse-phase column. The structure of the compound was established as N(delta)-(5-methyl-4-oxo-2-imidazolin-2-yl)-L-ornithine on the basis of an analysis of the spectral data and chemical degradation. This was confirmed by comparing the NMR spectrum of the metabolite with that of the compound synthesized by treating methylglyoxal and N(alpha)-acetyl-L-arginine. The substance did not show any antimicrobial activity against bacteria, fungi and yeasts by the agar plate method, but exhibited a weak preventive effect on cucumber mildew disease in a pot test.

Propeptin, a new inhibitor of prolyl endopeptidase produced by Microbispora. I. Fermentation, isolation and biological properties.

Propeptin, an inhibitor of the prolyl endopeptidase isolated from the mycelium of Microbispora sp. SNA-115, is an atypical cyclic peptide antibiotic. It was purified by column chromatographies on silica gel and Sephadex LH-20 and high performance liquid chromatography using an ODS column. Propeptin has the molecular formula of C113H142N26O27 and consists of nineteen amino acids. Propeptin inhibited prolyl endopeptidase of the genus Flavobacterium competitively when Z-Gly-Pro-pNA was used as a substrate. The inhibitor constant (Ki) was 0.70 microM.

SNA-8073-B, a new isotetracenone antibiotic inhibits prolyl endopeptidase. I. Fermentation, isolation and biological properties.

SNA-8073-B, an inhibitor of prolyl endopeptidase isolated from the broth filtrate of Streptomyces sp. SNA-8073, is a new isotetracenone antibiotic. It was purified by ethyl acetate extraction, silica gel column chromatography and high performance liquid chromatography on ODS column. SNA-8073-B has the molecular formula of C20H16O5 and is a stereoisomer of SNA-8073-A (fujianmycin B, rubiginone A2). SNA-8073-B inhibited prolyl endopeptidase of Flavobacterium non-competitively (IC50 = 8.9 microM) when Z-Gly-Pro-pNA was used as a substrate, but SNA-8073-A did not show any inhibition even at 60 microM.

Cryobacterium psychrophilum gen. nov., sp. nov., nom. rev., comb. nov., an obligately psychrophilic actinomycete to accommodate "Curtobacterium psychrophilum" Inoue and Komagata 1976.

"Curtobacterium psychrophilum," proposed by Inoue and Komagata in 1976, is a psychrophilic gram-positive irregular rod isolated from Antarctic soil. This organism grew optimally at 9 to 12 degrees C and did not grow at higher than 18 degrees C. Chemotaxonomic characteristics of this organism were the presence of 2,4-diaminobutyric acid in the cell wall and menaquinone-10 as the predominant respiratory quinone. The cellular fatty acid profile, which contained a significant amount of an anteiso-branched monounsaturated acid, 12-methyl tetradecenoic acid, was a distinctive characteristic of this organism and was reasonable for adaptation to low temperature. Phylogenetic analysis based on 16S ribosomal DNA sequences revealed that this organism was positioned at a separate branch in the family Microbacteriaceae, actinomycetes with group B peptidoglycan. We propose the name Cryobacterium psychrophilum gen. nov., sp. nov. for this organism. The type strain is JCM 1463 (= IAM 12024 = ATCC 43563 = IFO 15735 = NCIMB 2068).

Purification and characterization of a 15 kDa protein (p15) produced by Helicosporium that exhibits distinct effects on neurite outgrowth from cortical neurons and PC12 cells.

We have found that a 15 kDa protein (p15) produced by a fungus of Helicosporium genus induced characteristic morphological changes on neurites extending from rat cerebral cortex neurons in culture. In the presence of p15, neurite elongation from cortical neurons was markedly inhibited, and they extended short, slender, and less branched neurites. Laminin-induced promotion of neurite outgrowth was also dramatically suppressed. In contrast, p15 promoted nerve growth factor (NGF)-induced neurite outgrowth from PC12 cells, although treatment of cells with p15 alone had little effect. Partial amino acid sequence analysis of p15 revealed that it had limited homology to plant lectins. These results suggest that the mechanism of neurite outgrowth was considerably different between cortical neurons and PC12 cells and that p15 modulated neurite outgrowth in cell type-specific manners.

Cytotoxic benzyl dihydroflavonols from Cudrania tricuspidata.

Three new dihydroflavonols, gericudranins A-C were isolated from the stem bark of Cudrania tricuspidata. They were identified as 6,8-di-p-hydroxybenzyltaxifolin, 8-p-hydroxybenzyltaxifolin and 6-p-hydroxybenzyltaxifolin, respectively, by means of spectral studies. These compounds were cytotoxic to human tumor cell lines, such as CRL 1579 (skin), LOX-IMVI (skin), MOLT-4F (leukemia), KM12 (colon) and UO-31 (renal) in culture, with ED50 values of 2.7-31.3 micrograms ml-1.

Agromyces mediolanus sp. nov., nom. rev., comb. nov., a species for "Corynebacterium mediolanum" Mamoli 1939 and for some aniline-assimilating bacteria which contain 2,4-diaminobutyric acid in the cell wall peptidoglycan.

In the course of identifying aniline-assimilating bacteria, researchers found some gram-positive strains that contain 2,4-diaminobutyric acid in their cell wall peptidoglycans and menaquinone 12 as the predominant menaquinone. "Corynebacterium mediolanum" and "Flavobacterium dehydrogenans" also are known to contain 2,4-diaminobutyric acid in their cell walls, as well as menaquinone 12, but the taxonomic position of these organisms has not been established previously. We found that the aniline-assimilating strains, together with "C. mediolanum" and "F. dehydrogenans," belong to a single species of the genus Agromyces, as determined by phenotypic characteristics, DNA-DNA relatedness data, and 16S ribosomal DNA sequence similarity data. The name Agromyces mediolanus sp. nov., nom. rev., comb. nov., is proposed for these organisms. The type strain of A. mediolanus is strain JCM 3346 (= ATCC 14004 = NCIMB 7206).

Sparoxomycins A1 and A2, new inducers of the flat reversion of NRK cells transformed by temperature sensitive Rous sarcoma virus. II. Isolation, physico-chemical properties and structure elucidation.

Sparoxomycins A1 and A2, isolated from the fermentation broth and mycelium of Streptomyces sparsogenes SN2325, are new inducers of the flat reversion of NRK cells transformed by temperature sensitive Rous sarcoma virus. Sparoxomycins A1 and A2 were isolated by active carbon chromatography, centrifugal partition chromatography (CPC), ODS column chromatography and preparative HPLC. The structure of sparoxomycins were determined by spectroscopic evidences. Stereochemical assignments of these inducers were executed from the analyses of CD spectra.

Costunolide and dehydrocostus lactone as inhibitors of killing function of cytotoxic T lymphocytes.

Costunolide and dehydrocostus lactone were isolated from an extract of mokko (Saussurea lappa Clarke) as inhibitors of killing activity of cytotoxic T lymphocytes (CTL). Mokko lactone was also isolated as an inactive compound from the extract. The structure-activity relationship indicated that alpha-methylene-gamma-butyrolactone is required for the inhibitory effect. Costunolide markedly inhibited the granule exocytosis and the production of inositol phosphates in response to anti-CD3 monoclonal antibody (mAb) stimulation at a concentration that did not affect the binding of anti-CD3 mAb. Tyrosine phosphorylation induced by crosslinking of CD3 molecules was significantly inhibited by costunolide in a dose-dependent manner. These results suggest that costunolide inhibits the killing activity of CTL through preventing the increase in tyrosine phosphorylation in response to the crosslinking of T-cell receptors.

Antibacterial substance produced by Streptococcus faecium under anaerobic culture.

A facultative anaerobe isolated from Korean domestic soil produced an antibacterial substance under strict anaerobic conditions. Based on the morphological and biochemical tests, and cellular fatty acid profiles, the anaerobe was identified as Streptococcus faecium. An antimicrobial compound produced from the S. faecium was identified as 3,7,12-trihydroxy-24-cholanic acid methylester on the basis of its physico-chemical analysis. This substance had potent antibacterial activities against a test organism harboring multiple antibiotic resistance markers, and a variety of pathogenic bacteria. The isolated S. faecium produced lactic acid as well as the antibiotic compound under the anaerobic conditions.

1'-Acetoxychavicol acetate as an inhibitor of phagocytosis of macrophages.

We screened extracts of edible plants for inhibitors of phagocytosis by peritoneal exudate macrophages. 1'-Acetoxychavicol acetate was isolated from the ethyl acetate extract of Languas galanga, and this compound strongly inhibited phagocytosis at an IC50 value of 1.2 microM with negligible effects on pinocytosis and cell viability. Target(s) of 1'-acetoxychavicol acetate was suggested to be downstream of the signal transduction pathway that is mediated by protein kinase C.