RESUMO
Spectroscopic data define the structures of the flagranones A (2), B (3) and C (4) from the nematode-trapping fungus Duddingtonia flagrans. These antibiotics are structurally related to the farnesylated cyclohexenoxides of the oligosporon group recently isolated from the nematode-trapping fungus Arthrobotrys oligospora, and show similar antimicrobial activity.
Assuntos
Antibacterianos/química , Antinematódeos , Fungos Mitospóricos/química , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Benzoquinonas/química , Fungos/efeitos dos fármacosRESUMO
Fermentations of Streptomyces sp. E/784 produce low levels of the novel C-30 alkylthio-substituted ansamycin antibiotics naphthomycins J (9) and I (10), in addition to the more abundant C-30 hydroxylated analogues actamycin (1) and naphthomycin D (2) and C-30 chlorinated analogues naphthomycins H (3) and A (4). The addition of N-acetyl-L-cysteine to the fermentation medium substantially increases the production of the thionaphthomycins J and I at the expense of their chloro analogues H and A. Other thiols and thiol progenitors are similarly utilised, including N-acetyl-L-cysteine methyl ester which affords the known naphthomycin F (8) and its novel 2-demethyl homologue (7). The formation of thioansamycins from chloroansamycins and thiols in vivo is probably non-enzymic since similar conversions can be effected in vitro.
Assuntos
Aminobenzoatos/metabolismo , Antibacterianos/biossíntese , Antibacterianos/química , Naftoquinonas/química , Naftoquinonas/metabolismo , Streptomyces/metabolismo , Acetilcisteína/metabolismo , Antraquinonas/metabolismo , Antibacterianos/síntese química , Antibacterianos/metabolismo , Fermentação , Hidroxibenzoatos , Lactamas Macrocíclicas , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Naftoquinonas/síntese químicaRESUMO
An Actinomycete strain A499 belonging to the genera Amycolatopsis or Amycolata isolated from a Western Australian soil sample produced the cyclic decapeptide antibiotic quinaldopeptin (1), together with the actinotetraose hexatiglate (2), the hexa-ester of a novel non-reducing glucotetraose.
Assuntos
Actinomycetales/química , Crotonatos/química , Crotonatos/isolamento & purificação , Oligossacarídeos/química , Oligossacarídeos/isolamento & purificação , Actinomycetales/classificação , Actinomycetales/isolamento & purificação , Antibacterianos/química , Antibacterianos/isolamento & purificação , Sequência de Carboidratos , Fenômenos Químicos , Físico-Química , Equinomicina/análogos & derivados , Equinomicina/química , Equinomicina/isolamento & purificação , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Estrutura Molecular , Microbiologia do Solo , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosAssuntos
Antibacterianos/química , Oxigênio/química , Aminobenzoatos/química , Aminobenzoatos/metabolismo , Antraquinonas/química , Antraquinonas/metabolismo , Antibacterianos/biossíntese , Hidroxibenzoatos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Oxigênio/metabolismo , Streptomyces/química , Streptomyces/metabolismoRESUMO
Spectroscopic data define the structures of three new antibiotics, 4',5'-dihydro-oligosporon (4), hydroxyoligosporon (5) and 10',11'-epoxyoligosporon (6) from the nematode-trapping fungus Arthrobotrys oligospora, and confirm the structures of the recently reported antibiotics oligosporon (1) and oligosporol B (3). The absolute configuration of the substituted 7-oxabicyclo[4.1.0]hept-3-ene nucleus of these metabolites is determined by circular dichroic spectroscopy. Oligosporon (1) and its dihydro-derivative (4) represent the second and most complex structural type of nematocidal metabolite to be characterised from cultures of nematophagous fungi.
Assuntos
Antibacterianos/química , Antinematódeos/química , Compostos de Epóxi/química , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antinematódeos/isolamento & purificação , Antinematódeos/farmacologia , Dicroísmo Circular , Compostos de Epóxi/isolamento & purificação , Compostos de Epóxi/farmacologia , Haemonchus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Fungos Mitospóricos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Three Streptomyces isolates were identified as producing macrolide antibiotics of the bafilomycin or leucanicidin types during an evaluation of Australian actinomyces for the production of inhibitors of larval development in the parasitic nematode, Haemonchus contortus. Bafilomycins A1, B1, C1, and D were obtained from culture A239 and the 2-O-methyl-L-rhamnosyl derivative of bafilomycin A1, leucanicidin, from cultures A223 and A240. All these 'bafilolides' gave similar patterns of inhibition typified by an initial paralysis of newly hatched L1 larvae and a lethal toxicity within 24 h. LD50 values for inhibition of larval development of McMaster H. contortus ranged from 0.23 micrograms ml-1 for leucanicidin to 2.5 micrograms ml-1 for bafilomycin D. The bafilolides had broad spectrum nematocidal activity, being equi-potent as inhibitors of H. contortus, Trichostrongylus colubriformis and Ostertagia circumcincta larval development. Further, all bafilolides caused some inhibition of H. contortus L3 motility, with the semi-synthetic analogue, bafilomycin B2, the most potent inhibitor (LP50 against McMaster H. contortus 1.9 microgram ml-1). Nematode strains resistant to the known benzimidazole, levamisole and avermectin anthelmintics showed no cross resistance to the bafilolides, supporting the hypothesis that the bafilolides act by an independent mechanism.
Assuntos
Antibacterianos/farmacologia , Antinematódeos/farmacologia , Macrolídeos , Nematoides/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antinematódeos/química , Antinematódeos/isolamento & purificação , Relação Dose-Resposta a Droga , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Movimento/efeitos dos fármacos , Nematoides/crescimento & desenvolvimentoRESUMO
The larval haemolymph of the sheep blowfly Lucilia cuprina (Weidemann) contains a juvenile hormone binding protein with a Kd for racemic JH III of 33 +/- 6 nM. The density of the binding sites is 212 +/- 33 pmol/mg haemolymph protein. The binding protein is equally specific for JH III and methyl farnesoate. Some natural juvenoids were ranked for their ability to displace [3H]JH III with JH III > JH II > JH I > JH III acid > JH III diol > JHB3 = no detectable displacement. These data, together with displacement studies for 14 synthetic juvenoids, indicate some characteristics of the JH binding cleft. The binding protein is a high density lipophorin (density = 1.15 g/ml) and has subunit molecular weights of 228 kDa (apolipophorin I) and 70 kDa (apolipophorin II). The N-terminal amino acid sequences of the subunits have no discernible homology to any previously sequenced protein. Lipophorin-specific immunocytochemical staining occurs in a subset of fat body cells.
Assuntos
Proteínas de Transporte/química , Dípteros/química , Hormônios Juvenis/metabolismo , Lipoproteínas , Sequência de Aminoácidos , Animais , Ligação Competitiva , Proteínas de Transporte/metabolismo , Ligantes , Dados de Sequência Molecular , Estrutura Molecular , Peso Molecular , Ligação ProteicaRESUMO
Biosynthesis of the ansamycin antibiotic actamycin (2) was markedly increased by the addition of the precursor 3-amino-5-hydroxybenzoic acid (1) to the producing Streptomyces fermentation. Similar addition of the 4-chloro, 6-chloro, N-methyl and O-methyl analogues 4, 6, 5 and 7 of the amino acid 1 reduced actamycin production and did not yield structurally modified ansamycins. These results with the analogues 4, 5 and 7 indicate that the corresponding chlorine, N-methyl and O-methyl substituents present in the nuclei of various ansamycins are introduced at biosynthetic stages beyond the level of the amino acid 1.
Assuntos
Aminobenzoatos/metabolismo , Antibacterianos/biossíntese , Streptomyces/metabolismo , Antraquinonas/biossíntese , Fermentação , Hidroxibenzoatos , Lactamas Macrocíclicas , Espectroscopia de Ressonância Magnética , Relação Estrutura-AtividadeRESUMO
The metabolites of the predacious fungus Dactylaria lutea ROUTIEN include the anthraquinone macrosporin (2) and three hydroxylated 1,2,3,4-tetrahydro derivatives of this anthraquinone, altersolanol A (5), altersolanol B (4) and dactylariol (6). The structure and relative configuration of dactylariol are established from spectroscopic studies, and its absolute configuration is proposed as 1R, 2R, 3R by virtue of its co-occurrence with altersolanol B. Dactylarin, suggested by other authors to have the structure (1), is shown to be identical with altersolanol B (4).