Yuzuru Iwai

Absolute Configuration of Staurosporine By X-Ray Analysis

Abstract The stereostructure of staurosporine ( 1 ) was determined absolutely to be 2′ S , 3′ R , 4′ R , 6′ R -configurations by means of X-ray crystallographic analysis of 4′- N -methylstaurosporine methiodide ( 2 )

X-Ray crystal structure of staurosporine: a new alkaloid from a Streptomyces strain

The structure of staurosporine (1), a new alkaloid from a Streptomyces strain, has been established by X-ray crystallography.

Streptomyces avermectinius sp. nov., an avermectin-producing strain

We propose the establishment of a new species, Streptomyces avermectinius, based on characterization of strain MA-4680(T) and morphological and phylogenetic comparisons with closely related members of the genus Streptomyces. The 16S rDNA sequence was obtained from this strain and used to place it among Streptomyces species using the variable alpha region and the nearly complete 16S rDNA sequence. Four Streptomyces species were selected as related species from phenotypic data, three species from phylogenetic databases on alpha region sequences and two species from phylogenetic data using nearly complete 16S rDNA sequences. Analysis of DNA-DNA hybridization tests distinguished strain MA-4680(T) from these eight Streptomyces species. The type strain is strain MA-4680(T) (= ATCC 31267(T) = NRRL 8165(T)).

ANDRASTINS A-C, NEW PROTEIN FARNESYLTRANSFERASE INHIBITORS, PRODUCED BY PENICILLIUM SP. FO-3929

The structures of new protein farnesyltransferase inhibitors, andrastins A-C, were elucidated. The cyclopentane ring of andrastins exhibited keto-enol tautomerism, which made the structure hard to elucidate. Therefore, the structure of andrastin A was elucidated by INADEQUATE and 13C-13C couplings using 13C-labeled andrastin A. The absolute configuration of the p-bromobenzoyl derivative of andrastin A was elucidated by X-ray crystallographic analysis and its skeleton was shown to be ent-5 alpha,14 beta-androstane. The biosynthesis of andrastin A was also studied by the incorporation of 13C-labeled acetates. Though the andrastins had a common androstane skeleton, they were biosynthesized from a sesquiterpene and a tetraketide.

Studies on bacterial cell wall inhibitors. II. Inhibition of peptidoglycan synthesis in vivo and in vitro by amphomycin.

Abstract Amphomycin has been reported by the present authors to be a selective inhibitor of cell wall peptidoglycan synthesis in Bacillus cereus T (Ōmura, S., Tanaka, H., Shinohara, M., Ōiwa, R. and Hata, T. (1975) Chemotherapy 5, 365–369). Investigations were carried out to clarify the target of amphomycin. Amphomycin (10 μg/ml) lysed growing cells of B. cereus T, and inhibited peptidoglycan synthesis, accompanied by accumulation of uridine diphosphate- N -acetylmuramyl (UDP-MurNAc) peptides. The nucleotide precursors that accumulated in cells of Staphylococcus aureus FDA 209P in the presence of amphomycin were identified as UDP-MurNAc- L -Ala- D -Glu- L -Lys- D -Ala- D -Ala, UDP-MurNAc- L -Ala and UDP-MurNAc. In the experiments using a particulate enzyme system of Bacillus megaterium KM, amphomycin inhibited the polymerization of UDP-MurNAc- L -Ala- D -Glu-meso-diaminopimelic acid- D -Ala- D -Ala (UDP-MurNAc-pentapeptide) and UDP- N -acetylglucosamine, and also inhibited the formation of lipid intermediates, but did not inhibit the cross-linking, the last step of peptidoglycan synthesis. Unlike bacitracin, amphomycin did not lyse protoplasts of B. megaterium KM. We conclude that the site of action of amphomycin is the formation of MurNAc-(pentapeptide)-P-P-lipid from MurNAc-pentapeptide and undecaprenol (lipid) phosphate.

Structure of argifin, a new chitinase inhibitor produced by Gliocladium sp.

A new chitinase inhibitor, named argifin, was isolated from the cultured broth of a fungal strain Gliocladium sp. FTD-0668. Argifin was a water-soluble cyclic pentapeptide, and its structure was elucidated as cyclo(Nω-(N-methylcarbamoyl)-l-arginyl-N-methyl-l-phenylalanyl-β-l-aspartyl-β-l-aspartyl-d-alanyl). The IC50 value of argifin against blowfly (Lucilia cuprina) chitinase was 3.7 μM.

Stimulation of leucomycin production by magnesium phosphate and its relevance to nitrogen catabolite regulation.

Addition of magnesium phosphate [Mg3(PO4)2 x 8H2O] to a complex medium or to an ammonium ion-containing, chemically defined medium stimulated leucomycin production by Streptomyces kitasatoensis. Ammonium ions in high concentrations inhibited leucomycin production, but their limitation by magnesium phosphate led to the high production of the antibiotic.

Description of two novel species of the genus Kitasatospora omura et al. 1982, Kitasatospora cineracea sp. nov. and Kitasatospora niigatensis sp. nov.

Five actinomycete strains, SK-3255T, SK-3406T, SK-3412, SK-3421 and OM-5023, were isolated using a novobiocin-containing agar medium from soil samples. These strains produced long spore chains on aerial mycelium and contained LL- and meso-diaminopimelic acids (DAPs) in the cell wall. On the basis of morphological and chemotaxonomic characteristics and phylogenetic analysis, these five strains were classified into the genus Kitasatospora. DNA-DNA hybridization and comparison of physiological characteristics revealed that strains SK-3255T and SK-3406T differed from known species. Strains SK-3406T, SK-3412 and SK-3421 were regarded as the same species. Strain OM-5023 was identified as Kitasatospora griseola. Therefore, two novel species are proposed, Kitasatospora cineracea sp. nov. and Kitasatospora niigatensis sp. nov., with the type strains K. cineracea SK-3255T (= IFO 16452T = JCM 10915T = NRRL B-23134T) and K. niigatensis SK-3406T (= IFO 16453T = JCM 10916T = NRRL B-24135T).

Cytosaminomycins, new anticoccidial agents produced by Streptomyces sp. KO-8119. II. Structure elucidation of cytosaminomycins A, B, C and D.

Structures of novel anticoccidial antibiotics, cytosaminomycins A, B, C and D, were elucidated by NMR studies. Cytosaminomycins were shown to be nucleoside antibiotics related to oxyplicacetin. Their carboxylic acid moieties bonded to the cytosine residue were different from that of oxyplicacetin. The carboxylic acids contained in cytosaminomycins A, B, C and D were (E)-3-(methylthio)acrylic acid, 4-methylaminobenzoic acid, 3-methylcrotonic acid, and tiglic acid, respectively.

The structure of xanthoquinodin A1, a novel anticoccidial antibiotic having a new xanthone-anthraquinone conjugate system

The structure of the anticoccidial antibiotic xanthoquinodin A1(1), isolated from Humicola sp. FO-888, was elucidated by 1H- and 13C-NMR experiments. It contains a new type of xanthone and anthraquinone conjugate system.