Aureobasidins A to R were isolated from the fermentation broth of Aureobasidium pullulans R106. Aureobasidins are cyclic depsipeptide antibiotics with MW's ranging from 1, 070 to 1, 148. Aureobasidins showed high in vitro antifungal activity against Candida albicans.

View full abstract

Aureobasidin A, a new antifungal antibiotic, was isolated from the culture medium of Aureobasidium pullulans R106. Aureobasidin A was a cyclic depsipeptide consisting of eight α-amino acid units and one hydroxy acid unit. The structures of the units were found by acid hydrolysis of the antibiotic to be 2(R)-hydroxy-3(R)-methylpentanoic acid, β-hydroxy-N-methyl-L-valine, N-methyl-L-valine, L-proline, allo-L-isoleucine, N-methyl-L-phenylalanine, L-leucine, and L-phenyl-alanine. The sequence of the units was identified by NMR and FAB-MS of the products from the alkaline hydrolysis of aureobasidin A.

View full abstract

When grown in a defined medium containing 0.05% KBr, Saccharothrix aerocolonigenes ATCC 39243 produces a novel bromo analog of rebeccamycin. This new analog, designated bromorebeccamycin, has been isolated from the culture broth and purified by vacuum liquid chromatography and column chromatography. Spectroscopic data demonstrated that bromorebeccamycin has the same structure as rebeccamycin, except for the replacement of the two chlorine atoms by bromine atoms in the molecule. Bromorebeccamycin and rebeccamycin have a similar potency and activity against P388 leukemia in the murine model.

View full abstract

The morphology, chemotaxonomy, and cultural and physiological characteristics were examined on the five strains of actinomycetes which produce antiviral antibiotics, fluvirucin congeners. All strains have meso-2, 6-diaminopimelic acid in the cell wall. Four strains, Q464-31, L407-5, R359-5 and R516-16, belong to the maduromycetes since they have madurose in the whole cell. The remaining one strain, R869-90, has rhamnose but no madurose, and is a nocardioform actinomycete. These five strains were classified and designated as follows:
Strain Q464-31 (fluvirucin A₁ producer): Microtetraspora tyrrhenii sp, nov. (Actinomadura pusilla group).
Strain L407-5 (fluvirucin B₂ producer): A maduromycete.
Strain R359-5 (fluvirucin B₁ producer): Microtetraspora pusilla (Actinomadura pusilla group).
Strain R869-90 (fluvirucin A₂ producer): Saccharothrix mutabilis.
Strain R516-16 (fluvirucins B₂, B₃, B₄ and B₅ producer): A maduromycete.

View full abstract

Poststatin, a new inhibitor of prolyl endopeptidase (PEP) was discovered in the fermentation broth of Streptomyces viridochromogenes MH534-30F3. It was purified by Diaion HP-20, Sephadex LH-20 and YMC-gel (ODS-A) column chromatography and then isolated as a colorless powder. Poststatin has the molecular formula C₂₆H₄₇N₅O₇. The IC₅₀ value of poststatin against the PEP of partially purified porcine kidney was 0.03 μg/ml. It has low acute toxicity. No deaths occured after iv injection of 250 mg/kg of this agent to mice.

View full abstract

Poststatin, a new inhibitor of prolyl endopeptidase, has been isolated from the culture broth of Streptomyces viridochromogenes MH534-30F3. The structure of poststatin was defined as L-valyl-L-valyl-3-amino-2-oxovaleryl-D-leucyl-L-valine by analysis of spectral properties and chemical studies of poststatin and its derivatives. The α-keto group of postine in poststatin plays the most important role on the inhibitory mechanism.

View full abstract

In the course of screening soil organisms for new insecticidal metabolites, strain W719 was found to produce a group of metabolites active against the tobacco budworm Heliothis virescens. The active metabolites were purified by a combination of solvent partitioning and chromatographic steps, and the physico-chemical properties and insecticidal activity of the main components were determined. The two main components have MW's of 925 and 939, appear to belong to the macrocyclic lactam family of natural products, and possess significant insecticidal activity.

View full abstract

Structure-activity relationships in a series of (5R)-6-triazolylmethylene penems with potent β-lactamase inhibitory activity are described. In most cases, their in vitro synergistic activity with amoxycillin is superior to that of clavulanic acid, sulbactam and tazobactam (YTR 830). Against an Escherichia coli TEM-1 infection in mice, the compounds showed a broad range of potencies; an optimum polarity was found, however, which gave maximum potency.

View full abstract

The synthesis of new N-alkyl amphotericin B derivatives obtained in the Michael addition reaction of the antibiotic with N-substituted maleimides is described and in vitro biological data are presented.

View full abstract

A prototype sensitive strain of Pseudomonas aeruginosa (IR^S) was acclimatized in vitro to imipenem by serial transfers in broth containing increasing concentrations of the antibiotic up to 32 μg/ml. Serial subculture of the resistant progeny (IR1^r) in antibiotic-free solid media resulted in a "revertant" progeny (IR2^r) that retained resistance to imipenem. Acclimatization resistance to imipenem and the attempted reversion procedure affected colony morphology, growth rate, pigment production, growth at 42°C and glucose oxidation. SDS-PAGE analysis of the outer membrane, proteins revealed in strain IR1^r a complete loss of 6 proteins that were present in IR^s (85 kdaltons, 46 kdaltons or porin D1, 45.5 kdaltons or porin D2, 43 kdaltons or porin E, 21 kdaltons or protein H1 and 20.5 kdaltons or lipoprotein H2) and in strain IR2^r a complete loss of 3 proteins (46 kdaltons, 43 kdaltons, 20.5 kdaltons), while three others were found only in trace amounts (75 kdaltons, 45.5 kdaltons and 21 kdaltons). In the outer membranes of strains IR1^r and IR2^r an acquisition of a 56-kdalton protein was noted. Lipopolysaccharide chemical analysis revealed a marked, partially reversible increase in 2-keto-3-deoxyoctonate, total hexose and heptose constituents; readily extractable lipid chemical analysis and TLC, revealed a marked, partially reversible, increase in the phospholipid content of the outer membrane. Acclimatization resistance to imipenem was accompanied by cross-resistance to gentamicin, by partially reversible cross-resistance to moxalactam, carbenicillin and ticarcillin and by fully reversible cross-resistance to aztreonam. Sensitivity to azlocillin and polymyxin B remained unaltered. To explain this type of resistance to imipenem, an irreversible, non-inducible "loss" mutation mechanism, working in concert with a partially reversible mechanism, is proposed.

View full abstract

Large act I, III-homologous DNA fragments were isolated from genomic libraries of the strains that produce the benzoisochromanequinone antibiotics kalafungin and nanaomycin A methyl ester, Streptomyces tanashiensis strain Kala and Streptomyces sp. OM-173, respectively. These libraries were prepared in Escherichia coli JM108 by using a novel Streptomyces-E. coli bifunctional cosmid, pKU205, and screened with polyketide synthase genes (actI and III) for actinorhodin biosynthesis from Streptomyces coelicolor A3(2) as probes. The cloned DNA fragments (28 and 42kb) were analyzed by hybridization with DNA containing actinorhodin biosynthetic genes (actI, II, III, IV, VA, VB, VI and VII). Both fragments hybridized with the actI, III, VA and VI regions, but not with the actII, IV, VB and VII regions. The cloned fragment of S. tanashiensis DNA was analyzed by complementation tests with kalafungin-nonproducing mutants. Seven genes (kalI-VII), which correspond to seven steps in kalafungin biosynthesis, were found to be located on a 14 kb continuous DNA fragment. Five of the genes were located on the regions homologous to the genes for actinorhodin biosynthesis, but the other two genes were not. Although kalafungin is an intermediate or shunt product in actinorhodin biosynthesis in S. coelicolor A3(2), the genes for kalafungin biosynthesis in S. tanashiensis are not identical with those in S. coelicolor A3(2).

View full abstract

Two oligopeptides containing phosphinothricin were accumulated in the culture of bialaphos (BA) producer Streptomyces hygroscopicus SF1293 when large amount of BA was added to the culture at idio phase. One of the oligopeptides was a new substance, BA dimer (phosphinothricyl-alanyl-alanyl-phosphinothricyl-alanyl-alanine), and the other was a known substance called If (phosphinothricyl-alanyl-alanyl-phosphinothricin). Though BA none producing mutants which were blocked at the steps 1, 10 and 13, respectively in BA biosynthesis also converted BA to BA dimer and If, the mutants blocked at the step 11 (alanylation) could not curry out the conversion. Antibiotic activities of BA dimer and If were lower than 1/100 of BA.

View full abstract