ABSTRACT
On the basis of the one strain-many compounds (OSMAC) strategy, two new hygromycin A derivatives (3, 4), together with six known compounds were isolated from a medicinal plant inter rhizospheric Streptomyces in Pulsatilla chinensis. The structures of 3 and 4 were elucidated using NMR and HRESIMS analyses. A plausible biosynthetic pathway for these compounds was discussed. All the compounds were evaluated for their antimicrobial and cytotoxic activities. Compound 5 exhibited potent inhibitory activity against S. aureus and B. subtilis with the MICs of 16 and 8 µg ml-1, while 4 showed weak inhibitory activity against S. aureus.
Subject(s)
Cinnamates/isolation & purification , Hygromycin B/analogs & derivatives , Pulsatilla/microbiology , Soil/chemistry , Streptomyces/metabolism , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Cinnamates/pharmacology , Hygromycin B/isolation & purification , Hygromycin B/pharmacology , Microbial Sensitivity Tests/methods , Rhizosphere , Soil Microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/geneticsABSTRACT
The metabolic profile of Streptomyces sp. strain C34, isolated from the Chilean hyper-arid Atacama Desert soil, is dependent on the culture media used for its growth. The application of an OSMAC approach on this strain using a range of cultivation media resulted in the isolation and identification of three new compounds from the rare class of 22-membered macrolactone polyketides, named chaxalactins A-C (1-3). In addition, the known compounds deferroxamine E (4), hygromycin A (5), and 5â³-dihydrohygromycin A (6) were detected. The isolated compounds were characterized by NMR spectroscopy and accurate mass spectrometric analysis. Compounds 1-3 displayed strong activity against Gram-positive but weak activity Gram-negative strains tested.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Macrolides/isolation & purification , Streptomyces , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Cinnamates/chemistry , Cinnamates/isolation & purification , Escherichia coli/drug effects , Hygromycin B/analogs & derivatives , Hygromycin B/chemistry , Hygromycin B/isolation & purification , Listeria monocytogenes/drug effects , Macrolides/chemistry , Macrolides/pharmacology , Metabolome , Microbial Sensitivity Tests , Molecular Structure , Staphylococcus aureus/drug effects , Streptomyces/chemistry , Streptomyces/genetics , Streptomyces/metabolism , Vibrio/drug effectsABSTRACT
More than 400 compounds isolated from soil microorganisms, and catalogued in the antibiotic library of the Kitasato Institute for Life Sciences, were screened against African trypanosomes. Ten compounds were found to have selective and potent antitrypanosomal activity in vitro: aureothin, cellocidin, destomycin A, echinomycin, hedamycin, irumamycin, LL-Z 1272beta, O-methylnanaomycin A, venturicidin A and virustomycin A. Results of the in vitro assays using the GUTat 3.1 strain of Trypanosomal brucei brucei and the STIB900 strain of T. b. rhodesiense are presented. Cytotoxicity was determined using a human MRC-5 cell line. This is the first report of antitrypanosomal activities of the 10 microbial metabolites listed above.
Subject(s)
Trypanocidal Agents/isolation & purification , Trypanocidal Agents/pharmacology , Trypanosoma brucei brucei/drug effects , Alkynes/chemistry , Alkynes/isolation & purification , Alkynes/metabolism , Alkynes/pharmacology , Animals , Anthraquinones/chemistry , Anthraquinones/isolation & purification , Anthraquinones/metabolism , Anthraquinones/pharmacology , Cell Line , Chromones/chemistry , Chromones/isolation & purification , Chromones/metabolism , Chromones/pharmacology , Echinomycin/chemistry , Echinomycin/isolation & purification , Echinomycin/metabolism , Echinomycin/pharmacology , Hygromycin B/analogs & derivatives , Hygromycin B/chemistry , Hygromycin B/isolation & purification , Hygromycin B/metabolism , Hygromycin B/pharmacology , Macrolides/chemistry , Macrolides/isolation & purification , Macrolides/metabolism , Macrolides/pharmacology , Naphthoquinones/chemistry , Naphthoquinones/isolation & purification , Naphthoquinones/metabolism , Naphthoquinones/pharmacology , Soil Microbiology , Trypanocidal Agents/chemistry , Trypanocidal Agents/metabolism , Venturicidins/chemistry , Venturicidins/isolation & purification , Venturicidins/metabolism , Venturicidins/pharmacologyABSTRACT
Common bermudagrass, Cynodon dactylon, is a widely used warm-season turf and forage species in the temperate and tropical regions of the world. Improvement of bermudagrass via biotechnology depends on improved tissue culture responses, especially in plant regeneration, and a successful scheme to introduce useful transgenes. When the concentration of 6-benzylaminopurine was adjusted in the culture medium, yellowish, compact calluses were observed from young inflorescence tissue culture of var. J1224. Nine long-term, highly regenerable callus lines (including a suspension-cultured line) were subsequently established, of which six were used for biolistic transformation. Five independent transgenic events, with four producing green plants, were obtained following hygromycin B selection from one callus line. Three transgenic events displayed resistance to the herbicide glufosinate, and one of these showed beta-glucuronidase activity since the co-transformation vector used in the experiments contained both the gusA and bar genes.
Subject(s)
Biolistics/methods , Cynodon/genetics , Biotechnology/methods , Cell Line , Cynodon/embryology , Cynodon/physiology , Flowers/genetics , Flowers/physiology , Hygromycin B/isolation & purification , RegenerationABSTRACT
Immunosuppressants isolated from Streptomyces filipinensis and S. hygroscopicus were identified with pentalenolactone I and hygromycin A, respectively. The compounds as well as cyclosporin A showed immunosuppressant activity in the mixed lymphocyte reaction, and pentalenolactone I and cyclosporin A suppressed IL-2 production, however, hygromycin A did not. Hygromycin A may have immunosuppressant activity by a different mechanism from pentalenolactone I, cyclosporin A and tacrolimus.
Subject(s)
Cinnamates , Hygromycin B/analogs & derivatives , Hygromycin B/isolation & purification , Immunosuppressive Agents/isolation & purification , Pyrones/isolation & purification , Streptomyces/metabolism , Cyclosporine/pharmacology , Dose-Response Relationship, Drug , Hygromycin B/biosynthesis , Hygromycin B/pharmacology , Immunosuppressive Agents/pharmacology , Interleukin-2/antagonists & inhibitors , Interleukin-2/biosynthesis , Pyrones/metabolism , Pyrones/pharmacology , Species Specificity , Streptomyces/classification , Tacrolimus/pharmacologyABSTRACT
An affinity chromatography method was developed for the purification of hygromycin B from biological fluids. Lysozyme and alpha-lactalbumin were immobilized on an N-hydroxysuccinimide activated agarose support. Hygromycin B solubilized in water was bound by the proteins and subsequently eluted using 10 mM sodium citrate buffer, pH 4.0. Hygromycin B was purified from swine plasma, bovine serum and bovine milk samples using a combination of ion-exchange chromatography for initial clean-up of spiked biological samples followed by affinity chromatography. Thin layer chromatographic analysis of the isolated hygromycin B revealed one band with the same R(F) value as the hygromycin B standard.
