Characterization of the biosynthetic gene cluster for the oligosaccharide antibiotic, Evernimicin, in Micromonospora carbonacea var. africana ATCC39149.

Evernimicin (EV) belongs to the orthosomycin class of antibiotics and consists of several modified L- and D-deoxysugars containing unusual orthoester and glycosyl linkages and two orsellinic acid groups, one that is halogenated. The EV biosynthetic gene cluster from Micromonospora carbonacea var. africana ATCC39149 was localized by hybridization to a dTDP-D-glucose 4,6-dehydratase probe and a 120-kb region containing the EV biosynthetic cluster and surrounding regions has been sequenced. BLAST analysis has identified a type I polyketide synthase for orsellinic acid biosynthesis as well as enzymes required for L- and D-deoxyglucose and D-deoxymannose synthesis. In addition, genes involved in glycosyltransfer and resistance were identified. Insertional mutations in several biosynthetic genes blocked EV production, indicating a role for these genes in EV biosynthesis.

A novel macrolactam-trisaccharide antifungal antibiotic. Taxonomy, fermentation, isolation, physico-chemical properties, structure elucidation and biological activity.

A novel secondary metabolite SCH 42282 (1), with antifungal activity was isolated from the fermentation broth of a soil actinomycete identified as a Microtetraspora sp. The active compound was separated from the fermentation broth by butanol extraction and purified on a silica gel column and by multi-coil counter current chromatography. The compound was identified as a novel macrolactam trisaccharide related to SCH 38518 (4). The structure was established by hydrolysis of the parent compound and spectroscopic studies of the acetate derivative. The compound is active against Candida spp. (Geometric Mean MIC's. 18 micrograms/ml) but less active SCH 42729 (3). the disaccharide (Geometric Mean MIC's, > or = 10.7 micrograms/ml and SCH 38518 (4), the monosaccharide (Geometric Mean Mic's, 3.8 micrograms/ml.

A family of novel macrocyclic lactones, the saccharocarcins produced by Saccharothrix aerocolonigenes subsp. antibiotica. I. Taxonomy, fermentation, isolation and biological properties.

A nocardioform actinomycete, SCC 1886, isolated from a soil sample collected in Ohio was found to produce, in fermentation, six novel macrocyclic lactones, the saccharocarcins. The producing culture was identified as Saccharothrix aerocolonigenes subsp. antibiotica based on the formation of fragmenting substrate mycelia, aerial mycelia that coalesce to form aerial colonies, whole-cell hydrolysates that contain meso-diaminopimelic acid, galactose and rhamnose and physiological comparisons to type species of the genus. Peak production of the saccharocarcins occurred after 95 hours of fermentation in a starch rich medium. The compounds were isolated from the fermentation broth by solvent extraction and purified by HPLC. Isolated compounds were active against Micrococcus luteus, Staphylococcus aureus and Chlamydia trachomatis; none were cytotoxic at concentrations up to 1.0 microgram/ml.

A novel macrolactam-disaccharide antifungal antibiotic. Taxonomy, fermentation, isolation, physico-chemical properties, structure elucidation and biological activity.

A novel natural product (1), with antifungal activity was isolated from the culture broth of an actinomadurae. The active compound was separated from broth by n-butanol extraction and purified by silica gel and multicoil counter current chromatography. Physico-chemical data suggested the structure of this compound to be a novel macrolactam disaccharide related to Sch 38518 (3). The structure was determined by spectroscopic studies on the acetate derivative. It was active against Candida spp. (MIC's, 4 approximately 64 micrograms/ml) but less than the monosaccharide, Sch 38518 (MIC's, 1 approximately 16 micrograms/ml).

A novel class of platelet activating factor antagonists from Phoma sp.

Four novel platelet activating factor (PAF) antagonists, Sch 47918, Sch 49026, Sch 49027 and Sch 49028, were isolated from the fermentation broth of the fungal culture, Phoma sp. (ATCC 74077). The structures of these compounds were elucidated by spectroscopic methods. The structure and stereochemistry of the first isolated component, Sch 47918, were confirmed by single crystal X-ray diffraction analysis. Sch 49028, the most active component, was found to inhibit PAF-induced human platelet aggregation in vitro with an IC50 of 1.26 microM. However, this compound was inactive in vivo at 5 mg/kg, iv against PAF-induced bronchospasm in guinea pigs.

AT2433-A1, AT2433-A2, AT2433-B1, and AT2433-B2 novel antitumor antibiotic compounds produced by Actinomadura melliaura. Taxonomy, fermentation, isolation and biological properties.

Compounds AT2433-A1 (A1), AT2433-A2 (A2), AT2433-B1 (B1), and AT2433-B2 (B2) were isolated from the cultured broth of Actinomadura melliaura sp. nov. (SCC 1655). Structurally these materials are closely related to rebeccamycin (1), an indolocarbazole antitumor antibiotic. A1, A2, B1, and B2 were active against Staphylococcus aureus A9537, Streptococcus faecalis A20688, Streptococcus faecium (ATCC 9790), Micrococcus lutea (ATCC 9341), Bacillus subtilis (ATCC 6633). A1 and B1 were active against P388 leukemia in mice.

Sch 37137, a novel antifungal compound produced by a Micromonospora sp. Taxonomy, fermentation, isolation, structure and biological properties.

A new antifungal compound, Sch 37137, was isolated from the cultured broth of a Micromonospora sp., SCC 1792. Sch 37137 is structurally related to A 19009, a dipeptide previously discovered from a Streptomyces sp. The compound was weakly active against species of Candida and dermatophytes (mean MICs greater than or equal to 128 micrograms/ml) in Sabouraud dextrose, yeast-nitrogen and modified Eagles minimum essential media; however activity against Candida sp. (mean MICs greater than or equal to 12 micrograms/ml) and dermatophytes (mean MICs greater than or equal to 0.8 microgram/ml) significantly improved in MA medium.

Sch 36605, a novel anti-inflammatory compound. Taxonomy, fermentation, isolation and biological properties.

A novel anti-inflammatory compound, Sch 36605, belonging to the blasticidin family of nucleoside compounds was isolated from the fermentation filtrate of a Streptomyces sp. Sch 36605, as well as blasticidin S, demonstrated anti-inflammatory activity in the reverse passive Arthus reaction and the adjuvant arthritic rat at doses ranging between 1-10 mg/kg and 0.3-6.0 mg/kg, respectively. A minor component, Sch 366606, co-produced in the in the fermentation was isolated and identified as a known compound in the blasticidin family of compounds.

A novel tetracycline from Actinomadura brunnea. Fermentation, isolation and structure elucidation.

A novel tetracycline antibiotic, Sch 33256, was isolated from a culture broth of a new species of Actinomadura. The antibiotic was isolated by solvent extraction, Sephadex G-25 column chromatography and crystallization. The structure was determined by comparison of the spectra with that of chlortetracycline. Spectroscopic analysis of the compound yielded 2'-N-methyl-8-methoxychlortetracycline as the proposed structure.

A new tetracycline antibiotic from a Dactylosporangium species. Fermentation, isolation and structure elucidation.

An actinomycete identified as a Dactylosporangium sp. produces a new tetracycline, 4a-hydroxy-8-methoxychlortetracycline (Sch 34164). The addition of magnesium ions to complex fermentation media increased the antibiotic titers. Sch 34164 was isolated by solvent extraction and Sephadex G-25 column chromatography. The novel structure was proposed based on spectroscopic analysis. The shift of C-4a (35 to 77 ppm) and C-8 (140 to 163 ppm) in the 13C NMR as compared to chlortetracycline was indicative of the novel hydroxyl and methoxy substituents, respectively.

A novel phenazine antifungal antibiotic, 1,6-dihydroxy-2-chlorophenazine. Fermentation, isolation, structure and biological properties.

A novel, solvent extractable, antibiotic complex has been purified from the fermentation broth of an unusual member of the genus Streptosporangium. Two of the major components were isolated from the complex by alumina column chromatography. One of the components was identified as a previously reported compound, 1,6-dihydroxyphenazine. The other component was a novel chlorine containing phenazine, 1,6-dihydroxy-2-chlorophenazine, which exhibited broad spectrum antifungal activity in vitro against dermatophytes and Candida.

The hazimicins, a new class of antibiotics. Taxonomy, fermentation, isolation, characterization and biological properties.

The hazimicins, a new class of broad spectrum antibiotics with at least 2 active components (5 and 6), were isolated from the fermentation of Micromonospora echinospora var challisensis SCC 1411. The complex was separated from the broth by a solvent extraction procedure, and the individual components were separated by column chromatography. The two primary active components are isomers, with unique structures shown to be di-tyrosine analogs containing two isonitrile groups. The antibiotic has in vitro activity against Gram-positive and Gram-negative bacteria, and in vitro activity against yeasts and dermatophytes.

Kijanimicin (Sch 25663), a novel antibiotic produced by Actinomadura kijaniata SCC 1256. Fermentation, isolation, characterization and biological properties.

A novel antibiotic complex has been isolated form the fermentation broth of a new species of Actinomadura, A. kijaniata SCC 1256. The complex was separated form the broth by a solvent extraction procedure and consists of 1 major component, designated kijanimicin, and 3 minor components. Kijanimicin was isolated form the complex by column chromatography and/or preparative high pressure liquid chromatography. Structurally the compound is a unique, large acid enol antibiotic and possesses an unusual in vitro spectrum of activity against some Gram-positive and anaerobic microorganisms. In vivo it has also shown interesting activity against malaria.

Lipid composition in the classification of nocardiae and mycobacteria.

Ninety-six strains of aerobic actinomycetes with a type IV cell wall (major amounts of meso-diaminopimelic acid, arabinose, and galactose) were analyzed for the presence of mycolic acids and nocardomycolic acids. The method used was comparatively simple and permits the separation of these organisms into two groups: the mycobacteria and the nocardiae. In general, strains received as mycobacteria contained mycolic acids, confirming the generic assignment made by other methods. On the basis of nocardomycolic acid content, Mycobacterium brevicale, M. rhodochrous, and M. thamnopheos should be placed in the genus Nocardia, and on the basis of mycolic acid content, strains recently isolated from bovine farcy should be placed in the genus Mycobacterium. Nocardia farcinica should be considered a nomen dubium and N. asteroides should be considered the type species of the genus.