Microbial glycosylation of erythromycin A.

Erythromycin A (compound 1) was inactivated by Streptomyces vendargensis ATCC 25507 in fermentation. The inactivation product was isolated and characterized by nuclear magnetic resonance and mass spectroscopy as 2'-(O-[beta-D-glucopyranosyl])erythromycin A (compound 2). The MICs of compounds 1 and 2 were determined. Compound 2 lacked antibiotic activity when tested against several gram-positive pathogens, as well as S. vendargensis.

O-demethylpaulomycins A and B, U-77,802 and U-77,803, paulomenols A and B, new metabolites produced by Streptomyces paulus.

O-Demethylpaulomycin A (C33H44N2O17S), O-demethylpaulomycin B (C32H42N2O17S), paulomenol A (C29H43NO16), paulomenol B (C28H41NO16), and the hydrogen sulfide adducts of paulomycin A (U-77,802, C34H48N2O17S2), and paulomycin B (U-77,803, C33H46N2O17S2) have been isolated from fermentations of Streptomyces paulus strain 273. The structure of these compounds was determined by 1H and 13C NMR and fast atom bombardment mass spectrum spectroscopic techniques and degradative studies. The antibacterial properties of these new metabolites, which are related to paulomycins A and B (J. Antibiotics 35: 285-294, 1982), are briefly discussed.

Adenylylation of trospectomycin by crude enzyme preparations from Escherichia coli.

Employing osmotically shocked lysate of a spectinomycin resistant strain of Escherichia coli, trospectomycin, a new alkylspectinomycin, was adenylylated in the presence of adenosine 5'-triphosphate and magnesium ion. A highly resistant strain of E. coli was obtained by transforming a laboratory strain with a newly constructed plasmid consisting of pBR322 and a determinant for spectinomycin resistance originally found on a low copy number plasmid in E. coli strain NR79. The biologically inactive adenylylated trospectomycin was found to be trospectomycin 6-(5'-adenylate).

Structural relationships between senfolomycins and paulomycins.

Senfolomycins A and B (Antimicrob. Agents Chemother.-1965: 828-831, 1966) are two antibacterial agents with physico-chemical and biological properties similar to those of paulomycin. Recent studies indicate that senfolomycin A (C29H36N2O16S, MW 700) has molecular composition and fast atom bombardment MS fragmentation pattern identical to those of paulomycin E. Extensive NMR work indicates that the two antibiotics, which have been separated by HPLC and TLC, differ only in the stereochemistry of the OCH3 group present in their respective sugar moieties. Indirect evident suggests that senfolomycin B is dihydrosenfolomycin A (C29H38N2O16S, MW 702) and in this respect it is related to paulomycin F. The proposed structures for senfolomycins A and B are discussed.

New paulomycins produced by Streptomyces paulus.

Paulomycin A2 (C34H46N2O17S), paulomycin C (C32H42N2O17S), paulomycin D (C31H40N2O17S), paulomycin E (C29H36N2O16S) and paulomycin F (C29H38N2O16S) have been isolated from fermentations of Streptomyces paulus strain 273. The structure of these compounds was determined using NMR and mass spectroscopic techniques. The new paulomycins, like paulomycins A and B (J. Antibiotics 35: 285-294, 1982) are highly active mainly against Gram-positive organisms.

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.

Paulomycin-related antibiotics: paldimycins and antibiotics 273a2. Isolation and characterization.

The isolation of paulomycins A and B from fermentations of Streptomyces paulus has been reported earlier [J. Antibiotics 35: 285-294, 1982]. Further work on the antibiotics produced by S. paulus revealed the production of two paulomycin-related compounds, antibiotics 273a1 and 273a2 which were isolated by procedures involving extractions and chromatography over buffered silica gel. Antibiotic 273a1 which has been named paldimycin, was found to be a mixture of two materials, paldimycins A and B (antibiotics 273a1 alpha, and 273a1 beta). Similarly, antibiotic 273a2 was found to consist of antibiotic 273a2 alpha and antibiotic 273a2 beta. Paldimycin and antibiotic 273a2, which are produced by addition of two or one molecules of N-acetyl-L-cysteine, respectively, to paulomycins A and B, are active vs. Gram-positive bacteria.

Paldimycins A and B and antibiotics 273a2 alpha and 273a2 beta. Synthesis and characterization.

Paldimycin (antibiotic 273a1) and antibiotic 273a2 as well as their individual components, paldimycins A (273a1 alpha) and B (273a1 beta) and antibiotics 273a2 alpha and 273a2 beta were synthesized from paulomycin, paulomycin A and paulomycin B, respectively, by reacting with N-acetyl-L-cysteine. The semisynthetic antibiotics had chromatographic behavior (TLC, HPLC) and physical and chemical properties identical to the properties of the corresponding antibiotics produced by Streptomyces paulus.

Fermentation, isolation, characterization and structure of nitrosofungin.

The new antifungal agent nitrosofungin was isolated in high yields from a mixed culture of two organisms consisting of a bacterium of the genus Alcaligenes (UC 9152) and Streptomyces plicatus UC 8272. The bacterium produces the agent, the streptomycete enhances the production by providing a precursor or an inducer. Nitrosofungin in high concentrations inhibits a broad variety of pathogenic fungi in vitro. The agent is relatively non-toxic in small laboratory animals and high blood levels are obtained after either oral or systemic administration. Nitrosofungin is only the second N-nitrosohydroxylamine isolated from microbial sources to date. It has been identified as 2-N-nitrosohydroxylamino-1-propanol, an acidic and highly water-soluble compound.

Paulomycins A and B. Isolation and characterization.

Paulomycin A, C34H46N2O17S and paulomycin B, C33H44N2O17S are two antibiotics produced by Streptomyces paulus strain 273 (UC 5142). Both antibiotics, which are mainly active against a variety of Gram-positive bacteria, contain an isothiocyanate group and in this respect they are related to senfolomycins A and B and proceomycin.

Melinacidins II, III and IV. Structural studies.

The structures of melinacidines II, III and IV were determined by physicochemical methods. Melinacidine IV is considered to be identical to 11alpha,11alpha'-dihydroxychaetocin while melinacidins II and III are isomeric to chaetocin and verticillins A and B.

Microbial transformation of antibiotics. Clindamycin ribonucleotides.

Addition of clindamycin to whole-cell cultures of Streptomyces coelicolor Müller resulted in the loss of in vitro activity against organisms sensitive to clindamycin. Incubation of such culture filtrates with crude alkaline phosphatase generated a biologically active material identified as clindamycin. Fermentation broths containing inactivated clindamycin yielded clindamycin 3-ribonucleotides and clindamycin 3-phosphate the structure of which was established by physicochemical and enzymatic means. Attempts to transform clindamycin to clindamycin 3-ribonucleotides by lysates or partially purified enzyme preparations from S. coelicolor have failed.

Antibiotics produced by Streptomyces ficellus. I. Ficellomycin.

Ficellomycin is a new basic antibiotic produced by Streptomyces ficellus. Ficellomycin, C13H24N6O3, inhibits the growth of gram-positive bacteria in vitro and is effective in the treatment of experimental Staphylococcus aureus infections in mice.

Antibiotics produced by Streptomyces ficellus II. Feldamycin and nojirimycin.

Feldamycin, a new antibacterial agent, and nojirimycin, a previously described antibiotic have been isolated from cultures of Streptomyces ficellus. Feldamycin, C17H25N7O5, is an amphoteric compound which inhibits a variety of bacteria in vitro but is found to be ineffective in the treatment of experimental bacterial infections in mice. Nojirimycin (5-amino-5-deoxy-D-glucose) has been isolated previously from cultures of several species of streptomycetes.

Rancinamycins, metabolites produced by Streptomyces lincolnensis in sulfur-depleted media.

Rancinamycins I, II, III, and IV are secondary metabolites produced by Streptomyces lincolnensis in a sulfur-depleted culture medium. Rancinamycins I, and II, the main components of the mixture, show broad spectrum antibiotic activity in vitro. Subcutaneously injected or orally administered antibiotic afforded no protection for experimentally infected mice against lethal challenges of Staphylococcus aureus. Radioactive tracer studies failed to demonstrate that the rancinamycin were precursors in the biosynthesis of lincomycin.

Rancinamycins I, II, III and IV structural studies.

Rancinamycins are secondary metabolites produced by Streptomyces lincolnensis in a sulfur-depleted culture medium. The structures (except stereochemistry) of the main components of the rancinamycin-complex were determined by the use of IR, UV, PMR, and CMR spectra.

1-methylpseudouridine, a metabolite of Streptomyces platensis.

1-Methylpseudouridine is a new metabolite isolated from culture filtrates of Streptomyces platensis. The structure of this compound was determined from its physical and spectral properties.