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Y Odakura

Publications and source records attributed to Y Odakura.

14 recordsLinked to original sources
PubMed1984

Biosynthesis of astromicin and related antibiotics. I. Biosynthetic studies by bioconversion experiments.

Biosynthesis of astromicin, a unique pseudodisaccharide aminoglycoside antibiotic containing 1,4-diaminocyclitol component, was investigated by isolating a variety of possible precursor compounds from mutants of Micromonospora olivasterospora in which biosynthetic pathways for astromicin were blocked. Washed mycelia of M. olivasterospora mutants converted these compounds to astromicin, which was detected by thin-layer chromatography. Since astromicin possesses one glycyl and three methyl groups, [14C]glycine and [14C]methionine should be incorporated into precursors to form astromicin. To confirm the biosynthetic pathway, formation of labeled astromicin from the precursors was examined using [1-14C]-glycine or [methyl-14C]methionine. From above results, we propose the biosynthetic pathway for astromicin as shown in Fig. 2.

Aminoglycosides↗
PubMed1984

Biosynthesis of astromicin and related antibiotics. II. Biosynthetic studies with blocked mutants of Micromonospora olivasterospora.

An inosamine-idiotrophic mutant, KY11559, which produced no astromicin unless scyllo-inosamine was added to the fermentation medium, was isolated from Micromonospora olivasterospora. Biotransformation studies were performed with resting cells of this mutant and compounds assumed to be precursors of 1,4-diaminocyclitol (fortamine). Scyllo-inosose, scyllo-inosamine and FU-10 were converted to astromicin. A number of mutants blocked in the biosynthesis of astromicin were developed from M. olivasterospora, and the intermediates accumulated by these mutants were isolated and identified. Twenty-five blocked mutants were classified into 10 groups, based on their complementation patterns by cosynthesis experiments. Further, utilizing these blocked mutants and the isolated compounds, biotransformation analyses were performed. The results showed that the amination at position 4 in fortamine occurred after formation of the pseudodisaccharide. Subsequently, the aminosugar and aminocyclitol moieties were aminated, methylated, dehydroxylated, epimerized and acylated to produce astromicin. Thus it was demonstrated that the astromicin biosynthetic pathway has a unique feature which is not found in the biosynthesis of other aminoglycoside antibiotics.

Aminoglycosides↗
PubMed1983

Sagamicin and the related aminoglycosides: fermentation and biosynthesis. III. Isolation and characterization of Micromonospora sagamiensis mutants blocked in gentamicin C1 pathway.

Production of sagamicin and gentamicin C1 in Micromonospora sagamiensis was regulated by cobalt ion. In a parental strain, KY11510, cobalt ion stimulated gentamicin C1 production and suppressed sagamicin production. By ultraviolet light or N-methyl-N'-nitro-N-nitrosoguanidine treatment, six mutants blocked in gentamicin C1 biosynthesis were obtained from KY11510. These mutants were classified into two types. The first type, four mutants, produced no gentamicin C1 even when cobalt ion was added to the fermentation. The second type, two mutants, produced a small amount of gentamicin C1 when a high concentration of cobalt ion was added. Based on biotransformation experiments, these mutants appeared to be blocked at the 6'-C-methylation step in the biosynthesis of gentamicin C1. The mutants showed an increased production of sagamicin. In addition, cobalt ion stimulated sagamicin production in the mutants. The mechanism of cobalt regulation in the parent and the mutants is discussed.

Aminoglycosides↗
PubMed1982

Sagamicin and the related aminoglycosides: fermentation and biosynthesis. I. Biosynthetic studies with the blocked mutants of Micromonospora sagamiensis.

The mutants blocked in the gentamicin C1 production were derived from a sagamicin producing strain of Micromonospora sagamiensis. The intermediates produced by these mutants were isolated and properly identified. Comparing the biotransformation activities in the resting cells of the mutants with those of a DOS idiotroph, KY 11525, the blocked steps in sagamicin and gentamicin biosynthesis were proposed in each mutant. Mutant KY 11564 was found to produce gentamicin C2a (C-6'-epimer of gentamicin C2) together with gentamicin C1a and sagamicin. KY 11525 transformed gentamicin C2a into C2 and C1, whereas KY 11564 lacked the activity. KY 11565 produced gentamicin X2 and antibiotic G-418, and lacked 6'-amino substitution activities. KY 11566 appeared to be partially blocked in 6'-N-methylation activities, and the major products were gentamicin C2a and C1a. From these results, sagamicin biosynthesis in M. sagamiensis is discussed.

Aminoglycosides↗
PubMed1982

[Studies on the therapeutics of experimental toxoplasmosis. II. Effect of acetylspiramycin alone or in combination with an immunopotentiator (CSP-II) or sulfamethopyrazine on Toxoplasma multiplication in the heart of mice acutely and chronically infected with Toxoplasma gondii (author's transl)].

Normal mice acutely and chronically infected with the S-273 strain of T. gondii, were treated with acetylspiramycin (ASPM) alone, 8 mg/mouse/day, per os, or in combination with an immunopotentiator (CSP-II), 10 mg/mouse/day, intraperitoneally, or sulfamethopyrazine (SMPZ), 2 mg/mouse/day, per os, for a period of 4 weeks. In the acute cases, a 99.4% cyst reduction was obtained with ASPM alone and no cysts were seen in the brains of mice treated with ASPM in combination with CSP-II or SMPZ. The organisms were significantly eradicated in the brain and heart tissues of mice treated with ASPM alone or in combination with CSP-II or SMPZ as shown by subinoculation to normal mice and the negative latex hemagglutination titers of the recipient mice. In the chronic cases, a cyst reduction of 52.4% was obtained with mice treated with ASPM in combination with CSP-II. A cyst reduction of 34.6%, 32.9% and 20.8% was obtained in the ASPM alone, CSP-II alone and ASPM in combination with SMPZ treated groups, respectively. A comparative clearing of the organisms in the heart tissues of mice treated with ASPM in combination with CSP-II was obtained compared to the other treatment groups but not in the brains of all groups.

Adjuvants, Immunologic↗
PubMed1981

[Studies on the therapeutics of experimental toxoplasmosis. I. Effect of acetylspiramycin and spiramycin on the intracardiac Toxoplasma multiplication in mice infected with Toxoplasma gondii (author's transl)].

A total of 329 human serum samples were collected from the clinics of internal medicine of Obihiro city and its suburbs and were screened for Toxoplasma antibody level using the latex agglutination microtiter method (LA). Ninety-one (27.7%) were positive, 4 (1.2%) were equivocal and 234 (71.1%) were negative. Positive reactants were highest in the age group of 55-74 years old. A relatively high percentage on positive reactants was observed in patients with accompanying cardiac and cerebral disorders, i.e., 33.3% and 35.6%, respectively. ICR-JCL mice were infected with 10(2) tachyzoites of the S-273 strain of T. gondii intraperitoneally. Chronic cases were obtained from those mice which survived the first infection without any further challenge 1 month later. Therapy was carried out by administering acetylspiramycin or spiramycin per os at a dose of 8 mg/0.5 ml per mouse per day for 30 days. After the end of therapy, brain and heart emulsions were made, and passaged to clean mice and observed for 30 days. Antibody titers were also monitored during the course of treatment using the LA microtiter method. In the acute cases, antibody titers were observed to gradually increase from the end of treatment up to 10 weeks. Antibody titers of the chronic cases were maintained at high levels before the start of treatment and up to its termination. Most of the mice subinoculated with brain emulsions obtained from the acute cases, both in the control and treatment groups, died. However, all of the mice subinoculated with heart emulsions from both treatment groups, survived. In the chronic cases, all mice subinoculated with brain emulsions from all groups died. A few survived the heart passages from both treatment groups, however, they showed very high reactions to the LA microtiter method.

Adolescent↗
PubMed1977

Temperature sensitive R plasmids isolated from Proteus strains.

Out of 32 R plasmids isolated from Proteus strains, 17 were found to be temperature sensitive with respect to inheritance in E. coli cells. They were fi- and classified into incompatibility group T or V. Cells carrying T group Rms273 plasmid were temperature sensitive with respect to growth and conjugal transfer in both E. coli and Proteus. The V group YOR-10 plasmid was stable in Proteus even at 42 C. However, the loss frequency of YOR-10 plasmid in E. coli reached 100% after 4 hr of incubation at 42 C, in spite of stable inheritance at 25 C. Conjugal transfer of the YOR-10 plasmid in E. coli was also strongly inhibited at 42 C. It has been concluded that instability of V group R plasmids in E. coli is due to their thermosensitive inheritance in the progeny cells at high temperatures.

Escherichia coli↗
PubMed1974

R-factor mutant capable of specifying hypersynthesis of penicillinase.

The physical characteristics of a mutant, R(M201-2), capable of conferring high and stable ampicillion resistance was analyzed. The R(M201-2) and its parent R-factor deoxyribonucleic acid (DNA) could be isolated as an extrachromosomal and covalently closed circular form. Their buoyant densities were both 1.712 g/cm(3), and their molecular weights were about 82 x 10(6) and 64 x 10(6), respectively, when measured by CsCl and sucrose density gradient analyses. The contour lengths by electron microscopy were 35.9 +/- 0.6 and 31.0 +/- 0.6 mum, respectively. By using the extracted R-factor DNA, the mutant and parent characters were transformable to another Escherichia coli strain. The mutant R factor showed an increased amount of DNA even after conjugal transfer to Proteus. An increase in the size of R-factor DNA was thus considered to be the cause of the high level of ampicillin resistance.

Ampicillin↗
PubMed1973

Mutation of R factors capable of specifying hypersynthesis of penicillinase.

When strains harboring R factor and showing ampicillin (APC) resistance were inoculated on plates containing various concentrations of APC, mutants carrying various levels of APC resistance occurred at high frequencies. Increases in the level of APC resistance were due to a quantitative increase in the formation of penicillinase. By conjugation experiments and transduction analysis, the mutation was found to affect the gene (amp) governing APC resistance on the R factor. The R-factor mutants carrying high and stable APC resistance were conjugally transferred at the same frequency as their parent R factors, and the level of their resistance to drugs other than APC was not distinct from that conferred by their parents. Such R-factor mutants could easily be obtained from wild-type R factors carrying low APC resistance. The hypersynthesis of penicillinase by such R-factor mutants was considered to be due to the replication of the amp gene on the R factor at hyper-rates and the integration of multiple copies of the amp gene (amp-hyper) in the R-factor genome.

Ampicillin↗