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Biomedical subjects

R Oiwa

Publications and source records attributed to R Oiwa.

At least 19 recordsLinked to original sources

Screening for new antitrichomonal substances of microbial origin and antitrichomonal activity of trichostatin A.

In vitro and in vivo screening methods for new antitrichomonal substances were established. Primary screening is based on in vitro antitrichomonal activities of culture broths of actinomycetes isolated from soil. With secondary screening, after crude materials obtained from the cultured broths were administered orally to mice, excretion of antitrichomonal activity into urine was examined. Tertiary screening was done by examining therapeutic activity for experimental trichomoniasis in mice with Trichomonas foetus. Using the screening systems, a new antibiotic (setamycin)-producing strain was picked out among about six thousands soil isolates, and the therapeutic efficacy of KM-3851, which was identified as trichostatin A, was found. It was active against T. foetus both in vitro and in vivo.

Animals

Lustromycin, a new antibiotic produced by Streptomyces sp.

A new antibiotic, lustromycin, was isolated from the cultured broth of Streptomyces sp. SK-1071. It exhibits selective antibacterial activity against anaerobic bacteria including Clostridium sp. The molecular formula C32H38O13 as determined by high resolution mass spectrometry, and elemental analysis and the NMR spectrum suggest structural resemblance of this antibiotic to luminamicin, an anti-anaerobic antibiotic reported previously.

Anti-Bacterial Agents

Clostomicins, new antibiotics produced by Micromonospora echinospora subsp. armeniaca subsp. nov. I. Production, isolation, and physico-chemical and biological properties.

A soil isolate named as Micromonospora echinospora subsp. armeniaca subsp. nov. KMR-593 was found to produce at least five related antibiotics, clostomicins, active against Gram-positive bacteria including anaerobes. From the physico-chemical properties, one of these components was identified with lipiarmycin and others were found to be new antibiotics. Each component includes two chlorine atoms and the molecular weights of A and B2, C, and D are 1,058, 1,042 and 1,056, respectively. The structural differences were characterized by NMR analyses.

Aminoglycosides

Takaokamycin, a new peptide antibiotic produced by Streptomyces sp.

A new peptide antibiotic named takaokamycin was isolated from a fermentation broth of Streptomyces sp. AC-1978, a soil isolate. It exhibits antibacterial activity against some Gram-positive bacteria. The molecular weight was found to be 1,130 on the basis of elemental analysis, FD-mass spectrum and 1H and 13C NMR. Acid hydrolysate of takaokamycin contains isoleucine, threonine and unidentified amino acids.

Animals

Phosalacine, a new herbicidal antibiotic containing phosphinothricin. Fermentation, isolation, biological activity and mechanism of action.

Phosalacine, a new herbicidal antibiotic containing phosphinothricin was isolated from the culture filtrate of a soil isolate Kitasatosporia phosalacinea KA-338. It was a water soluble, amphoteric compound obtained as an amorphous powder (C14H28N3O6P, MW 365). The antibiotic exhibited antimicrobial activity against Gram-positive and Gram-negative bacteria and some fungi on a minimal medium and the activity was reversed by L-glutamine. It also showed herbicidal activity against alfalfa. It is suggested that phosalacine was decomposed to provide phosphinothricin after its incorporation into microbial or plant cells, and exhibited the antimicrobial and herbicidal activities by inhibiting glutamine synthetase with phosphinothricin although phosalacine itself hardly inhibited the enzyme.

Actinomyces

Studies on bacterial cell wall inhibitors. X. Properties of phosph-N-acetylmuramoyl-pentapeptide-transferase in peptidoglycan synthesis of Bacillus megaterium and its inhibition by amphomycin.

The phospho-N-acetylmuramoyl-pentapeptide-transferase from Bacillus megaterium KM was characterized by the transfer reaction. The particulate enzyme preparation had the activity to transfer phospho-N-acetylmuramoyl-pentapeptide from UDP-N-acetylmuramoyl-pentapeptide to undecaprenoid-1-ol-phosphate. The optimum pH for activity was about 8.5. The reaction required the presence of Mg2+ and an SH-protector. With 25 mm Mg2+ the maximum activity was observed. The reaction was reversible and so the addition of UMP decreased the formation of undecaprenoid-1-ol-diphospho-N-acetylmuramoyl-pentapeptide. Amphomycin inhibited non-competitively the transferase for the substrate UDP-N-acetylmuramoyl-pentapeptide.

Adenosine Triphosphate

Setamycin, a new antibiotic.

A new antibiotic, setamycin, was extracted from the mycelia of a rare actinomycete strain KM-6054. The antibiotic, the molecular formula of which was found to be C42H61NO12 (tentative), is a yellow powder showing activity against some fungi, trichomonads and weakly against Gram-positive bacteria.

Actinomycetales

Virantmycin, a new antiviral antibiotic produced by a strain of Streptomyces.

Virantmycin, a novel chlorine-containing antiviral antibiotic, has been isolated from Streptomyces nitrosporeus No. AM-2722. The active substance in culture broth is isolated as colorless needles by solvent extraction followed by high performance liquid chromatography on silicic acid. The molecular formula is C19H26NO3Cl (molecular weight 351) from the elemental analysis and mass spectrum. The antibiotic possesses antifungal activity and potent inhibitory activity against various RNA and DNA viruses.

Anti-Bacterial Agents

The site of inhibition of bacterial cell wall peptidoglycan synthesis by azureomycin B, a new antibiotic.

Azureomycin B (10 micrograms/ml), a new antibiotic from Pseudonocardia azurea nov. sp., caused the accumulation of lipid intermediate and inhibition of peptidoglycan synthesis in an invitro system using a particulate fraction from Bacillus megaterium KM with UDP-MurNAc-[3H]pentapeptide and cold UDP-GlcNac or cold UDP-MurNAc-pentapeptide and UDP-[3H]GlcNAc as substrates. At higher concentrations of azureomycin B (over 100 microgram/ml), lipid intermediate accumulation was also inhibited. When particulate fraction from Escherichia coli Y-10 and UDP-[14C[GlcNAc and cold UDP-MurNAc-pentapeptide were used, accumulation of lipid intermediate and inhibition of peptidoglycan synthesis were also observed. These results indicate that the primary target of azureomycin B is the transfer of the disaccharide peptide unit (GlcNAc-MurNAc-pentapeptide) from lipid-bound precursor to acceptor.

Actinomycetales

Avermectins, new family of potent anthelmintic agents: producing organism and fermentation.

The avermectins are a complex of chemically related agents which exhibit extraordinarily potent anthelmintic activity. They are produced by a novel species of actinomycete, NRRL 8165, which we have named Streptomyces avermitilis. The morphological and cultural characteristics which differentiate the producing organism from other species are described. The avermectins have been identified as a series of macrocyclic lactone derivatives which, in contrast to the macrolide or polyene antibiotics, lack significant antibacterial or antifungal activity. The avermectin complex is fully active against the gastrointestinal nematode Nematospiroides dubius when fed to infected mice for 6 days at 0.0002% of the diet. Fermentation development, including medium modification and strain selection, resulted in increasing the broth yields from 9 to 500 mug/ml.

Anthelmintics

Studies on bacterial cell wall inhibitors. VI. Screening method for the specific inhibitors of peptidoglycan synthesis.

A screening method was established for selecting new specific inhibitors of bacterial cell wall peptidoglycan synthesis. In the primary test, culture broths of soil isolates were selected based on relative microbial activity. A culture, to be retained, must be active against Bacillus subtilis and lack activities against Acholeplasma laidawii. In the secondary test, inhibitors of bacterial cell wall synthesis were identified by their ability to prevent the incorporation of meso-[3H]diaminopimelic acid but not to prevent the incorporation of L-[4C]leucine into the acid-insoluble macromolecular fraction of growing cells of Bacillus sp. ATCC 21206 (Dpm-). As the tertiary test, inhibitors with molecular weights under 1,000 were selected by passage through a Diaflo UM-2 membrane. By this screening procedure, six known antibiotics and one new one were picked out from ten thousand soil isolates.

Acholeplasma laidlawii