Arginomycin: production, isolation, characterization and structure.

Arginomycin is a new nucleoside antibiotic produced by Streptomyces arginesis. Arginomycin, C18H28N8O5, which inhibits the growth of Gram-positive bacteria and fungi in vitro, is structurally related to blasticidin S and found to be relatively non-toxic.

Isolation and structure of antibiotic U-68,204, a new thiolactone.

A new thiolactone-containing antibiotic U-68,204 was found to be produced by a soil actinomycete identified as Streptomyces thiolactonus UC 8478 (NRRL 15,439). The production, isolation, structure determination as well as the physical, spectroscopic and antibacterial properties of this C13H17NO3S compound are here reported. On the basis of these data, the antibiotic was identified as the 10-carboxamide of thiotetromycin.

Microbial hydroxylation of novobiocin and related compounds.

A new soil actinomycete (UC 5762, NRRL 11111) was found to transform novobiocin to 11-hydroxynovobiocin. The product was isolated by solvent extraction and column chromatography, and identified by IR, UV, 1H NMR and 13C NMR spectroscopy. Related structures (8,9-dihydronovobiocin, novobiocic acid and chlorobiocin) were similarly transformed to their corresponding C-11 hydroxylated analogues. The microbial process is superior to chemical (selenium dioxide) oxidation which yielded a mixture of 11-hydroxy- and 11-oxonovobiocin.

Development of a GC-MS method for quantitation of 2,3-dinor-TxB2 and determinations of the daily urinary excretion rates in healthy humans.

Tetradeuterated 2,3-dinor-thromboxane B2 (2,3-dinor-TxB2) of high isotopic purity was prepared. This compound was used as internal standard in the development of a method for quantitation of 2,3-dinor-TxB2 in human urine based on gas chromatography--mass spectrometry with multiple ion detection. The accuracy of the method is about +/- 5% at the levels encountered when urine from normal healthy individuals was analyzed. The daily urinary excretion of 2,3-dinor-TxB2 in twenty normal healthy males and females was 457 +/- 210 (mean +/- SD) and 444 +/- 160 (mean +/- SD) ng/24 hrs respectively. The diurnal and day-to-day variations were found to be relatively small.

Preparation of two dinor-PGI2 metabolites from 6-keto-PGF1 alpha by Mycobacterium rhodochrous.

The transformation of 6-keto-PGF1 alpha to two prostacyctin metabolites, 2,3-dinor-6-keto-PGF1 alpha (I) and 2,3-dinor-6,15-diketo-13,14-dihydro-PGF1 alpha (II) by Mycobacterium rhodochrous UC-6176 is described. The finding that the bacterium oxidized 6-keto-PGF1 alpha to the 6,15-diketo metabolite II shows that it contains 15-hydroxy prostaglandin dehydrogenase and delta 13 reductase enzyme systems.

Synthesis and biological activity of 9-deoxo-9-methylene and related prostaglandins.

A number of PGE analogs have been synthesized in which the C-9 carbonyl group has been replaced by an exo-methylene group. These chemically stable 9-deoxo-9-methylene-PGEs exhibit biological profiles very similar to their less stable PGE relatives. 9-Deoxo-16,16-dimethyl-9-methylene-PGE2 (7) retains the useful uterine-stimulating potency of 16,16-dimethyl-PGE2 but is approximately 300 times less enteropooling in the rat. In preliminary clinical trials, 7 has shown efficacy for pregnancy termination by the oral and vaginal routes of administration, as well as relative freedom from gastrointestinal side effects.

Synthesis of thromboxane B2 metabolites.

This paper reports the synthesis of 11-dehydrothromboxane B2 methyl ester (II), 15-dehydrothromboxane B2 methyl ester (III), 15-dehydro-13, 14-dihydrothromboxane B2 (XII) and 2,3-dinorthromboxane B2 methyl ester (XV). These compounds, as their free acids, have been reported to be thromboxane metabolites.

Microbial formation of 4-thiouracil.

A soil organism identified as Streptomyces libani var. soldani was found to produce 4-thiouracil. The product was isolated in a yield of 150 mug/ml of filtered beer and characterized by C-13 magnetic resonance and high-resolution mass spectroscopy. The product has a broad antibacterial spectrum but low specific activity.

The scope and potential of antibiotic conversion by microorganisms.

Almost 50 antibiotics have been reported to be modified microbiologically and the changes observed were grouped into 16 types of reactions. Most of the products of the reactions were antibiotically inactive, several have assumed a considerable clinical significance and others are of real or potential economic value. The catalysis in most instances has been effected by whole cells and in a few cases the respective enzymes were isolated, purified and crystallized.

Metabolism of beta-methylaspartate by a pseudomonad.

A bacterium was isolated from soil which utilizes threo-beta-methyl-l-aspartate, certain other amino acids, and a variety of organic substances as single energy sources. It is, or closely resembles, Pseudomonas putida biotype B. The ability of this organism to rapidly decompose such amino acids is dependent on inducible enzyme systems. Dialyzed cell-free extracts of this bacterium metabolize beta-methylaspartate only when catalytic amounts of alpha-ketoglutarate, or pyruvate, and pyridoxal phosphate are also present. The main products formed from beta-methylaspartate under these conditions are alpha-aminobutyrate, carbon dioxide, and alpha-ketobutyrate. When l-aspartate is substituted for beta-methylaspartate in this system, it is converted mainly to alanine and carbon dioxide. beta-Methyloxalacetate is decarboxylated, and the resulting alpha-ketobutyrate is converted enzymatically in the presence of glutamate to alpha-aminobutyrate which accumulates. The added keto acids are converted, in part, to the corresponding amino acids probably by transamination. The data indicate that beta-methylaspartate is converted to alpha-aminobutyrate, and aspartate to alanine, by a circuitous transamination-beta-decarboxylation-transamination sequence rather than by a direct beta-decarboxylation.