RESUMEN
A new spectinabilin derivative (1) was isolated from the fermentation broth of the ant-derived Streptomyces sp. 1H-GS5, and the structure was elucidated by extensive spectroscopic analysis. Compound 1 showed cytotoxicity against human tumor cell lines A549, HCT-116, and HepG2 with IC50 values of 9.7, 12.8, and 9.1 µg/ml, respectively, which was relative higher than that of spectinabilin.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Hormigas/microbiología , Pironas/aislamiento & purificación , Pironas/farmacología , Streptomyces/química , Animales , Antineoplásicos/química , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Células Hep G2 , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Fragmentos de Péptidos/química , Pironas/química , Sustancia P/análogos & derivados , Sustancia P/químicaRESUMEN
Milbemycin oxime has been commercialized as effective anthelmintics in the fields of animal health, agriculture, and human infections. Currently, milbemycin oxime is synthesized by a two-step chemical reaction, which involves the ketonization of milbemycins A3/A4 to yield the intermediates 5-oxomilbemycins A3/A4 using CrO3 as catalyst. Due to the low efficiency and environmental unfriendliness of the ketonization of milbemycins A3/A4, it is imperative to develop alternative strategies to produce 5-oxomilbemycins A3/A4. In this study, the atmospheric and room temperature plasma (ARTP) mutation system was first employed to treat milbemycin-producing strain Streptomyces bingchenggensis, and a mutant strain BC-120-4 producing milbemycins A3, A4, B2, and B3 as main components was obtained, which favors the construction of genetically engineered strains producing 5-oxomilbemycins. Importantly, the milbemycins A3/A4 yield of BC-120-4 reached 3,890 ± 52 g/l, which was approximately two times higher than that of the initial strain BC-109-6 (1,326 ± 37 g/l). The subsequent interruption of the gene milF encoding a C5-ketoreductase responsible for the ketonization of milbemycins led to strain BCJ60 (∆milF) with the production of 5-oxomilbemycins A3/A4 and the elimination of milbemycins A3, A4, B2, and B3. The high 5-oxomilbemycins A3/A4 yield (3,470 ± 147 g/l) and genetic stability of BCJ60 implied the potential use in industry to prepare 5-oxomilbemycins A3/A4 for the semisynthesis of milbemycins oxime.
Asunto(s)
Antihelmínticos/metabolismo , Macrólidos/metabolismo , Ingeniería Metabólica , Mutagénesis , Streptomyces/genética , Streptomyces/metabolismo , Eliminación de Gen , Inestabilidad GenómicaRESUMEN
Three new cyclopentenone derivatives (1-3) were isolated from the rare actinomycete Actinoalloteichus nanshanensis NEAU 119. Their structures were elucidated by extensive spectroscopic analysis. Compound 1 showed moderate cytotoxic activity against human lung adenocarcinoma cell line A549, human leukemia cell line K562, and human renal carcinoma cell line ACHN with an IC50 of 14.67, 11.87, and 23.36 µg ml(-1), respectively.
Asunto(s)
Actinobacteria/química , Antineoplásicos/aislamiento & purificación , Ciclopentanos/aislamiento & purificación , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma del Pulmón , Antineoplásicos/química , Antineoplásicos/farmacología , Ciclopentanos/química , Ciclopentanos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Ficus/microbiología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Estructura Molecular , RizosferaRESUMEN
Streptomyces bingchenggensis is a soil bacterium that produces milbemycins, a family of macrolide antibiotics that are commercially important in crop protection and veterinary medicine. In addition, S. bingchenggensis produces many other natural products including the polyether nanchangmycin and novel cyclic pentapeptides. To identify the gene clusters involved in the biosynthesis of these compounds, and better clarify the biochemical pathways of these gene clusters, the whole genome of S. bingchenggensis was sequenced, and the transcriptome profile was subsequently investigated by microarray. In comparison with other sequenced genomes in Streptomyces, S. bingchenggensis has the largest linear chromosome consisting of 11 936 683 base pairs (bp), with an average GC content of 70.8%. The 10 023 predicted protein-coding sequences include at least 47 gene clusters correlated with the biosynthesis of known or predicted secondary metabolites. Transcriptional analysis demonstrated an extremely high expression level of the milbemycin gene cluster during the entire growth period and a moderately high expression level of the nanchangmycin gene cluster during the initial hours that subsequently decreased. However, other gene clusters appear to be silent. The genome-wide analysis of the secondary metabolite gene clusters in S. bingchenggensis, coupled with transcriptional analysis, will facilitate the rational development of high milbemycins-producing strains as well as the discovery of new natural products.
Asunto(s)
Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Genoma Bacteriano , Microbiología Industrial , Streptomyces/genética , Streptomyces/metabolismo , Antibacterianos/biosíntesis , Proteínas Bacterianas/química , Cromosomas Bacterianos , Genes Bacterianos , Datos de Secuencia Molecular , Familia de Multigenes , Análisis de Secuencia por Matrices de Oligonucleótidos , Metabolismo Secundario/genética , Análisis de Secuencia de ADN , Transducción de Señal/genética , Streptomyces/química , Streptomyces/clasificaciónRESUMEN
Two new piperidine alkaloids, streptazones E (1) and F (2), were isolated from Streptomyces sp. NEAU-Z4. Their structures were elucidated on the basis of MS and NMR analysis.
Asunto(s)
Alcaloides/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Piperidinas/aislamiento & purificación , Streptomyces/química , Alcaloides/química , Alcaloides/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Células Hep G2 , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Piperidinas/química , Piperidinas/farmacologíaRESUMEN
A novel macrocyclic lactone (1) was isolated from the fermentation broth of Streptomycesmicroflavus neau3, and the structure was elucidated by extensive spectroscopic analysis. Compound 1 showed high acaricidal activity against adult mites (IC(50)=11.1 µg mL(-1)), and nematocidal activity against Caenorhabditis elegans (IC(50)=17.4 µg mL(-1)), especially the acaricidal activity against mite eggs with an IC(50) of 37.1 µg mL(-1), which was relative higher than that of the commercial acaricide and nematocide milbemycins A(3)/A(4).
Asunto(s)
Acaricidas/farmacología , Antinematodos/farmacología , Caenorhabditis elegans/efectos de los fármacos , Lactonas/farmacología , Compuestos Macrocíclicos/farmacología , Ácaros/efectos de los fármacos , Acaricidas/química , Acaricidas/aislamiento & purificación , Animales , Antinematodos/química , Antinematodos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Fermentación , Insecticidas/química , Insecticidas/aislamiento & purificación , Insecticidas/farmacología , Lactonas/química , Lactonas/aislamiento & purificación , Compuestos Macrocíclicos/química , Compuestos Macrocíclicos/aislamiento & purificación , Conformación Molecular , Estereoisomerismo , Streptomyces/química , Streptomyces/metabolismo , Relación Estructura-ActividadRESUMEN
A new quinoline derivative, methyl 8-(3-methoxy-3-methylbutyl)-2-methylquinoline-4-carboxylate (1), was isolated from the endophytic strain Streptomyces sp. neau50, and the structure was elucidated by extensive spectroscopic analysis. Compound 1 showed cytotoxicity against human lung adenocarcinoma cell line A549 with an IC(50) value of 29.3 µg mL(-1).
Asunto(s)
Antineoplásicos/química , Quinolinas/química , Streptomyces/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/toxicidad , Línea Celular Tumoral , Humanos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Quinolinas/aislamiento & purificación , Quinolinas/toxicidadRESUMEN
Four new doramectin congeners, 1-4, were isolated from Streptomyces avermitilis NEAU1069. The structures of 1-4 were elucidated on the basis of spectroscopic analysis, including 1D- and 2D-NMR as well as HR-ESI-MS, ESI-MS, UV, and IR, and comparison with literature data. All compounds exhibited noticeable acaricidal and insecticidal activities. Especially compound 2 was found to be the most potent pesticide of the compounds evaluated with the IC(50) values of 10.2, 65.1 and 124.4 µg/ml against adult two-spotted spider mites (Tetranychus urticae Koch), two-spotted spider mite eggs, and Mythimna separata, respectively, which are comparable to those of commercial pesticide milbemycin A(3)/A(4) as positive reference.
Asunto(s)
Acaricidas/aislamiento & purificación , Insecticidas/aislamiento & purificación , Ivermectina/análogos & derivados , Streptomyces/metabolismo , Acaricidas/química , Acaricidas/farmacología , Animales , Insecticidas/química , Insecticidas/farmacología , Ivermectina/química , Ivermectina/aislamiento & purificación , Ivermectina/farmacología , Estructura Molecular , Mariposas Nocturnas/efectos de los fármacos , Tetranychidae/efectos de los fármacos , Tetranychidae/crecimiento & desarrolloRESUMEN
Streptomyces bingchenggensis is a soil-dwelling bacterium producing the commercially important anthelmintic macrolide milbemycins. Besides milbemycins, the insecticidal polyether antibiotic nanchangmycin and some other antibiotics have also been isolated from this strain. Here we report the complete genome sequence of S. bingchenggensis. The availability of the genome sequence of S. bingchenggensis should enable us to understand the biosynthesis of these structurally intricate antibiotics better and facilitate rational improvement of this strain to increase their titers.
Asunto(s)
Antibacterianos/biosíntesis , Éteres/metabolismo , Genoma Bacteriano , Análisis de Secuencia de ADN , Compuestos de Espiro/metabolismo , Streptomyces/genética , Proteínas Bacterianas/genética , Genoma Bacteriano/genética , Macrólidos/metabolismo , Datos de Secuencia Molecular , Streptomyces/clasificación , Streptomyces/metabolismoRESUMEN
A new tetrahydrobenzofuranone derivative, strefuranone A (1), was isolated from Streptomyces sp. HS-NF-853. The structure of the compound was elucidated on the basis of MS and extensive NMR analysis.
Asunto(s)
Benzofuranos/aislamiento & purificación , Streptomyces/metabolismo , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Benzofuranos/química , Benzofuranos/metabolismo , Benzofuranos/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Fermentación , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Streptomyces/químicaRESUMEN
A new prenylated indole derivative 3-acetonylidene-7-prenylindolin-2-one (1) was isolated from the endophytic actinobacterium Streptomyces sp. neau-D50, together with four known hybrid isoprenoids, 7-isoprenylindole-3-carboxylic acid (2), 3-cyanomethyl-6-prenylindole (3), 6-isoprenylindole-3-carboxylic acid (4) and 7,4'-dihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (5). The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with data from the literature. Compounds 1 and 2 demonstrated strong cytotoxic activities against human lung adenocarcinoma cell line A549 with an IC50 of 3.3 and 5.1 µg mL(- 1), respectively, which are comparable to that of the positive control doxorubicin (4.2 µg mL(- 1)). Furthermore, compounds 1-4 exhibited potent antifungal activity against phytopathogenic fungi Colletotrichum orbiculare, Phytophthora capsici, Corynespora cassiicola and Fusarium oxysporum.
Asunto(s)
Antifúngicos/aislamiento & purificación , Alcaloides Indólicos/aislamiento & purificación , Streptomyces/química , Antifúngicos/química , Antifúngicos/farmacología , Colletotrichum/efectos de los fármacos , Fusarium/efectos de los fármacos , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacología , Indoles , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Phytophthora/efectos de los fármacos , Enfermedades de las Plantas/microbiología , Raíces de Plantas/microbiología , Prenilación , Glycine max/microbiologíaRESUMEN
Four novel cyclopentenone derivatives (1-4), characterising a cyclopentenone ring conjugated with a 1,8-dioxadecalin, were isolated from rare actinobacterial strain Actinoalloteichus nanshanensis sp. nov. NEAU 119. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis. Bioassays indicated that compounds 1-4 showed low cytotoxicities against human leukaemia cell line K562 and human renal carcinoma cell line ACHN. To the best of our knowledge, this is the first example of isolation of C11 cyclopentenones from actinomycetes.
Asunto(s)
Actinomycetales/química , Antiinfecciosos/aislamiento & purificación , Ciclopentanos/aislamiento & purificación , Antiinfecciosos/química , Antiinfecciosos/farmacología , Candida albicans/efectos de los fármacos , Línea Celular Tumoral , Ciclopentanos/química , Ciclopentanos/farmacología , Humanos , Estructura Molecular , Rhizoctonia/efectos de los fármacos , Especificidad de la Especie , Análisis Espectral , Staphylococcus epidermidis/efectos de los fármacosRESUMEN
Neaumycin, a new 30-membered macrolide featuring an internal diester bridge, a molecular architecture that is unprecedented among known macrolide natural products, was isolated from a soil actinomycete strain Streptomyces sp. NEAU-x211. The structure of neaumycin was elucidated on the basis of comprehensive mass and NMR spectroscopic interpretation, including the relative stereochemistry of four independent coupling systems.
Asunto(s)
Macrólidos/química , Streptomyces/química , Macrólidos/aislamiento & purificación , Estructura Molecular , EstereoisomerismoRESUMEN
Borrelidin has high and specific antifungal activity against Phytophthora sojae . To explore the antifungal mechanism of borrelidin against P. sojae , the relationship between the antifungal activity of borrelidin and the concentration of threonine was evaluated. The results demonstrated that the growth-inhibitory effect of borrelidin on the growth of P. sojae was antagonized by threonine in a dose-dependent manner, suggesting that threonyl-tRNA synthetase (ThrRS) may be the potential target of borrelidin. Subsequently, the inhibition of the enzymatic activity of ThrRS by borrelidin in vitro was confirmed. Furthermore, the detailed interaction between ThrRS and borrelidin was investigated using fluorescence spectroscopy and circular dichroism (CD), implying a tight binding of borrelidin to ThrRS. Taken together, these results suggest that the antifungal activity of borrelidin against P. sojae was mediated by inhibition of ThrRS via the formation of the ThrRS-borrelidin complex.
Asunto(s)
Antifúngicos/farmacología , Phytophthora/efectos de los fármacos , Antifúngicos/metabolismo , Alcoholes Grasos/metabolismo , Alcoholes Grasos/farmacología , Proteínas Fúngicas/antagonistas & inhibidores , Proteínas Fúngicas/metabolismo , Phytophthora/enzimología , Phytophthora/metabolismo , Unión Proteica , Treonina/metabolismo , Treonina-ARNt Ligasa/antagonistas & inhibidores , Treonina-ARNt Ligasa/metabolismoRESUMEN
In this study, an endophytic Streptomyces sp. neau-D50 with strong antifungal activity against Phytophthora sojae was isolated from healthy soybean root, using an in vitro screening technique. A bioactivity-guided approach was then employed to isolate and determine the chemical identity of bioactive constituents with antifungal activity from strain neau-D50. The structure of the antifungal metabolite was elucidated as borrelidin on the basis of spectral analysis. To our knowledge, this is the first report that borrelidin has strong antifungal activity against dominant race 1 of P. sojae with EC(50) and EC(95) of 0.0056 and 0.026 mg/L, respectively. The values were respectively 62.5- and 262.3-fold lower than those of the commercial fungicide metalaxyl, which has been used to treat soybean seed for the control of P. sojae . The in situ bioassays demonstrated that borrelidin at 10 mg/L reduced P. sojae race 1 lesions on soybean seedlings by 94.72% without affecting root growth. Thus, borrelidin might be a promising candidate for new antifungal agents against P. sojae.