Ann C. Horan

KIJANIMICIN (Sch 25663), A NOVEL ANTIBIOTIC PRODUCED BY ACTINOMAD URA KIJANIATA SCC 1256

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.

Use of red-shifted dyes in a fluorescence polarization AKT kinase assay for detection of biological activity in natural product extracts

Kinases are an important therapeutic target for drug discovery, and many cancer chemotherapeutic agents have been derived from natural product sources. Natural product samples, however, have the likelihood of assay interference, particularly at elevated test concentrations. The authors developed a competitive fluorescence polarization (FP) assay using red-shifted fluorophores for the AKT kinase and demonstrated utility for testing concentrated natural product extracts. A set of 7 actinomycetes cultures containing indolocarbazoles, known nonselective kinase inhibitors, and a control set of 22 nonproducing indolocarbazole cultures were evaluated. Using red-shifted dyes (Cy3B™ or Cy5™), the authors identified active samples with minimal interference up to the extract concentrations that are 3 times nonextracted culture levels. In contrast, a significant number of interferences were observed using either a fluorescein competitive FP assay or a [33P]ATP Flashplate assay. This work demonstrates that one can screen natural product extracts at high concentrations successfully using FP technology with red-shifted dyes. (Journal of Biomolecular Screening 2004:52-61)

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. Journal of Industrial Microbiology & Biotechnology (2001) 27, 386–392.

A Piecemeal Description of Streptomyces griseus (Krainsky) Waksman and Henrici

SUMMARY: Forty-six of the 48 strains named Streptomyces griseus in our collection have in common a distinctive pattern of properties and are believed to represent a recognizable taxonomic group, or aggregate, of this polytypic species. Seventy-seven additional strains bearing 51 different species names were found to possess the same pattern of characteristics. The distinguishing properties of this aggregate are described and compared with those of S. albus, S. fradiae and S. somaliensis.

Nocardia dassonvillei, a macroscopic replica of Streptomyces griseus.

SUMMARY: Twenty-six strains of Nocardia dassonvillei (Brocq-Rousseu) Liegard & Landrieu from the soil and from infections of man and animals are described, and a pattern of characteristics for their identification and differentiation from N. asteroides, N. brasiliensis, N. caviae, N. madurae and N. pelletieri is presented. Strains of N. dassonvillei resembled strains of Streptomyces griseus (Krainsky) Waksman & Henrici in the macroscopic appearance of their growth and in many of the physiological properties examined.

A Novel Antibiotic-Producing Actinomadura, Actinomadura kijaniata sp. nov.

A new species of Actinomadura, Actinomadura kijaniata, was isolated from African soil. This organism differs from other species of Actinomadura in that it forms deep green vegetative mycelia and white, curled aerial mycelia that fragment into long chains of smooth-walled, elliptical spores and produces a complex of novel acid enol antibiotics. Whole cells contain meso-diaminopimelic acid and madurose but lock nitrogenous phospholipids. This species can utilize a wide variety of carbohydrates, grow in the presence of numerous antibiotics, and actively hydrolyze many organic compounds. The type strain of A. kijaniata is SCC 1256 (= ATCC 31588).

Micromonospora rosaria sp. nov., nom. rev., the Rosaramicin Producer

The name of the producer of the macrolide antibiotic rosaramicin, Micromonospora rosaria NRRL 3718T (T = type strain), was not included on the Approved Lists of Bacterial Names because the original publication did not contain a full description of this strain. Following its first appearance in the literature and its subsequent availability, M. rosaria NRRL 3718 frequently appeared in studies as a comparative organism when new antibiotic-producing species of Micromonspora were described. Therefore, we formally revive the name M. rosaria, present a full species description, and designate strain NRRL 3718 as the type strain.

Actinoplanes caeruleus sp. nov. a Blue-Pigmented Species of the Genus Actinoplanes

A new, antibiotic-producing species of Actinoplanes, Actinoplanes caeruleus, was isolated from soil. This organism formed irregular to globose sporangia which upon wetting dehisced to release spherical to oval, polarly flagellated motile spores. It contained arabinose and xylose as characteristic whole-cell sugars. This organism differed from other species of the genus Actinoplanes by forming deep blue vegetative mycelial pigments, by the absence of diaminopimelic acid on the cell wall, by its ability to hydrolyze adenine and hypoxanthine, by its resistance to lysozyme, and by its inability to utilize L-arabinose, D-xylose, and succinate as sole carbon sources. The type strain of A. caeruleus is strain SCC 1014 (= ATCC 33937).

Nebularine from a novelMicrobispora sp.

SummaryNebularine has now been isolated from a novelMicrobispora sp., identified as a new mesophilic species. An efficient method for the isolation of nebularine using Droplet Counter Current Chromatography is described.

Naturally produced isocoumarins: inhibitors of calmodulinsensitive cyclic guanosine 3′,5′-monophosphate phosphodiesterase

SummaryThree isocoumarins have been isolated from a strain ofStreptoverticillium sp. and all inhibit the calmodulin-sensitive cyclic guanosine 3′,5′-monophosphate phosphodiesterase (EC 3.1.4.17, Boehringer Mannheim). Two of the compounds, 6,8-dihydroxy-7-methoxy-3-methyl isocoumarin and 6,7,8-trihydroxy-3-methyl isocoumarin have previously been isolated fromStreptomyces. The third fermentation product, 6,8-dihydroxy-3-methyl isocoumarin, was also found as a metabolite ofCeratocystis minor, a fungal species associated with the blue stain disease of pine [2,3].