A novel bone resorption inhibitor, A-75943 isolated from Streptomyces sp. SANK 61296.

A novel bone resorption inhibitor, A-75943, was isolated from Streptomyces sp. SANK 61296. Its structure was determined to be (1"S,2'R,3"S,4S',5"S)-2-[(3",5"- dimethyl-2"-oxocyclohexan-1"-yl)-6'-oxotetrahydropyran-4'-yl ]acetamide by spectral analyses and chemical conversion of cycloheximide. A-75943 inhibited bone resorption in vitro in a concentration-dependent manner with an IC50 of 0.35 microM, and also displayed an inhibitory effect on bone resorption in thyroid and parathyroid-extracted rats.

A-72363 A-1, A-2 and C, novel heparanase inhibitors from Streptomyces nobilis SANK 60192. I. Taxonomy of producing organism, fermentation, isolation and structure elucidation.

Novel heparanse inhibitors, A72363 A-1, A-2, and C, were isolated from the culture filtrate of Streptomyces nobilis SANK 60192 by column chromatography on various resinous adsorbents, followed by preparative anion exchange HPLC. Spectroscopic studies revealed that they are diastereomers of siastatin B, a neuraminidase inhibitor.

Novel microbial metabolites of the phoslactomycins family induce production of colony-stimulating factors by bone marrow stromal cells. I. Taxonomy, fermentation and biological properties.

Three metabolites were isolated from the culture broth of an actinomycete strain identified as Streptomyces platensis SANK 60191, that induce the production of colony-stimulating factors (CSFs) by stromal cell line KM-102 at ED50 concentrations from 40 to 200 ng/ml. The compounds induced quantities of granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) comparable to those induced by interleukin-1, a strong CSF inducer. These metabolites were called leustroducsins (A, B and C) and were later found to be structurally related to phoslactomycins. This is the first report of CSF inducing activity by members of the phoslactomycin class.

Milbemycins alpha 11, alpha 12, alpha 13, alpha 14 and alpha 15: a new family of milbemycins from Streptomyces hygroscopicus subsp. aureolacrimosus. Taxonomy, fermentation, isolation, structure elucidation and biological properties.

Streptomyces hygroscopicus subsp. aureolacrimosus SANK 60286 produces a new family of milbemycins, named milbemycins alpha 11, alpha 12 [corrected], alpha 13, alpha 14 and alpha 15, together with other milbemycins. Their structures are 3-methyl-2-butenoyloxy and 3-methylbutyroyloxy derivatives at C-4a of milbemycins A3 and A4, or 3-methyl-2-pentenoyloxy derivative at C-4a of milbemycin A3, respectively. Milbemycin alpha 14, 3-methyl-2-butenoyloxy derivative, especially possesses a potent acaricidal activity.

Isolation of trehalamine, the aglycon of trehazolin, from microbial broths and characterization of trehazolin related compounds.

Trehalamine, (3aR,4R,5S,6S,6aS)-2-amino-4-(hydroxymethyl)-3a,5,6,6a- tetrahydro-4H-cyclo-pent[d]oxazole-4,5,6-triol (1) and D-glucose were obtained by acid hydrolysis of trehazolin (3), a trehalase inhibitor produced by actinomycetes. More vigorous hydrolytic treatment of trehazolin afforded an aminocyclitol, (1R,2S,3R,4S,5R)-5-amino-1- (hydroxymethyl)cyclopentane-1,2,3,4-tetraol (2). Trehalamine, the aglycon of trehazolin, was also found in the culture broths of two trehazolin producing strains, Micromonospora sp. SANK 62390 and Amycolatopsis sp. SANK 60791. These trehazolin related compounds trehalamine (1) and 2 were poor inhibitors of trehalase (1; IC50 1.8 x 10(-4) M, 2; > 5.0 x 10(-4) M). On the other hand they inhibited more potently rat intestinal sucrase (1; IC50 6.8 x 10(-5) M) and sweet almond beta-glucosidase (2; IC50 5.6 x 10(-6) M) than trehazolin.

Matlystatins, new inhibitors of typeIV collagenases from Actinomadura atramentaria. I. Taxonomy, fermentation, isolation, and physico-chemical properties of matlystatin-group compounds.

During the course of a screening for inhibitors of typeIV collagenases, new metabolites, designated matlystatins, have been isolated from an actinomycete strain, which was identified as a strain of Actinomadura atramentaria. Matlystatins were composed of five congeners, which were separated and purified by n-butanol extraction and chromatography.

Galacardins A and B, new glycopeptide antibiotics.

A strain of actinomycetes identified as Saccharothrix sp. SANK 64289 was found to produce new antibiotics, galacardins A and B. Their physico-chemical properties showed that they were new members of glycopeptide antibiotics. They were structurally related to beta-avoparcin but differed from it only in sugar composition. Though beta-avoparcin does not contain galactose, galacardins A and B did contain two and one moles of galactose, respectively. They showed strong antimicrobial activity against Gram-positive bacteria and also showed excellent in vivo protective activity against Staphylococcus aureus infection in mice.

Helvecardins A and B, novel glycopeptide antibiotics. I. Taxonomy, fermentation, isolation and physico-chemical properties.

A strain of actinomycetes identified as Pseudonocardia compacta subsp. helvetica produced new glycopeptide antibiotics, helvecardins A and B. They were isolated from culture broth mainly by affinity chromatography of D-alanyl-D-alanine and preparative HPLC. The physico-chemical properties of helvecardins A and B showed that they resemble each other. Though helvecardin A was structurally related to beta-avoparcin, it clearly differed in the presence of an O-methyl moiety in its NMR spectrum.

Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity. I. Taxonomy, fermentation, isolation and physico-chemical properties.

A strain of actinomycetes identified as Streptomyces flavidovirens produced new antibiotics, mureidomycins (MRD's) A approximately D, specifically active against Pseudomonas aeruginosa. They were isolated from the culture filtrate by successive column chromatographies such as Amberlite XAD-2 and CG-50, Whatman DE-52 and Toyopearl HW-40. They were amphoteric white powders and soluble in methanol and water. Their molecular weights and molecular formulae in parentheses were 840 (C38H48N8O12S), 842 (C38H50N12S), 897 (C40H51N9O13S) and 899 (C40H53N9O13S), respectively. m-Tyrosine and two unknown substances were detected by amino acid analyses as their common constituents. MRD's A and C contained uracil but MRD's B and D dihydrouracil instead of uracil.

Chloropolysporins A, B and C, novel glycopeptide antibiotics from Faenia interjecta sp. nov. I. Taxonomy of producing organism.

Strain SANK 60983, an actinomycete isolated from a soil sample, was found to produce the new glycopeptide antibiotics, chloropolysporins A, B and C. Short chains of spores occur in the both aerial and substrate hyphae. meso-Diaminopimelic acid is present in the cell wall and galactose and arabinose in the whole-cell hydrolysate. Mycolic acid is absent. On the basis of the morphological, cultural and physiological characteristics, this strain was determined to be a new species of Faenia designated Faenia interjecta sp. nov. The type strain of F. interjecta Okazaki and Enokita is SANK 60983.

Propioxatins A and B, new enkephalinase B inhibitors. I. Taxonomy, fermentation, isolation and biological properties.

A soil isolate of actinomycete, strain SANK 60684, was found to produce new enkephalinase B inhibitors, propioxatins A and B. The presence of both LL- and meso-2,6-diaminopimelic acid, glycine and galactose in the cell wall assigned this strain to genus Kitasatosporia. From the morphological, cultural and physiological characteristics, this strain was determined to be Kitasatosporia setae. The Ki values of propioxatins A and B were 1.3 X 10(-8)M and 1.1 X 10(-7)M, respectively, for enkephalinase B. All other proteases examined except aminopeptidases, which were slightly inhibited, were not inhibited by these two compounds.

Terferol, an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase. I. Isolation and characterization.

Terferol, a new inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase (EC 3.1.4.17, cAMP-PDE), was isolated from the cultured broth of Streptomyces showdoensis SANK 65080. It was found to have the molecular formula C19H16O3 and to possess inhibitory activity not only against cAMP-PDE but also against cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP-PDE) from various rat tissues. The terferol concentration required for 50% inhibition of cAMP-PDE was 0.82 microM.

Aculeximycin, a new antibiotic from Streptosporangium albidum. I. Taxonomy of producing organism and fermentation.

A soil isolate of actinomycete, strain TI-1, was found to produce a new antibiotic aculeximycin which killed insects as well as inhibited the growth of bacteria, yeasts and molds in vitro. Yellowish gray colonies on agar media, formation of spherical to oval sporangia at the tip of aerial mycelium and the presence of meso-diaminopimelic acid and madurose in the cell wall ascribed this strain to genus Streptosporangium. From its morphological, cultural and physiological characteristics, the strain was determined to be S. albidum. Production of aculeximycin was carried out by conventional submerged culture: the highest antibiotic titer obtained was 1,250 micrograms/ml.

Taxonomy of actinomycetes capable of hydroxylation of ML-236B (compactin).

Three actinomycetes having capability of 3 beta-hydroxylation of ML-236B were isolated from soil samples collected in Australia. Strain SANK 62781 was identified as Nocardia autotrophica. Strain SANK 62881 and strain SANK 62981 were identified as new subspecies of N. autotrophica for which the name N. autotrophica subsp. canberrica and N. autotrophica subsp. amethystina are proposed, respectively. The type strains of N. autotrophica subsp. canberrica and N. autotrophica subsp. amethystina are ATCC 35203 and ATCC 35204.

Mycoplanecins, novel antimycobacterial antibiotics from Actinoplanes awajinensis subsp. mycoplanecinus subsp. nov. I. Taxonomy of producing organism and fermentation.

Strain No. 41042, an actinomycete isolated from a soil sample, was found to produce 5-azacytidine and new antibiotics, mycoplanecins. Yellowish brown to yellowish orange color of colonies on agar media, formation of globose to subglobose sporangia bearing motile spores and presence of meso- and hydroxy-diaminopimelic acid and glycine in the cell wall ascribed this strain to genus Actinoplanes. From its morphological, cultural and physiological characteristics, this strain was determined to be a new subspecies of Actinoplanes awajinensis and designated as A. awajinensis subsp. mycoplanecinus subsp. nov. Production of mycoplanecins was carried out by conventional submerged culture: the highest antibiotic titer obtained was 145 micrograms/ml.

New antibiotic, isohematinic acid. I. Taxonomy of producing organism, fermentation and isolation.

New antibiotic, isohematinic acid, was found in the culture broth of an actinomycete strain SANK 61681, which was identified as a strain of Actinoplanes philippinesis. Fermentation of isohematinic acid was performed by conventional submerged culture in a 600-liter fermentor. Isolation of isohematinic acid was performed by adsorption of the antibiotic from the culture filtrate on a column of Diaion HP-20 followed by elution with aqueous acetone and extraction with ethyl acetate. Isohematinic acid was finally crystallized from hot methanol.