RESUMEN
A new insecticidal meroterpenoid, named sesquicillin F (1), has been isolated from a culture broth of Mariannaea macrochlamydospora FKI-4735, together with 4-hydroxy-5,6-dimethylpyran-2-one (2). Compounds 1 and 2 were insecticidally active against Halyomorpha halys at 1 ppm.
Asunto(s)
Hypocreales/química , Insecticidas/toxicidad , Animales , Insectos , Insecticidas/química , Japón , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Microbiología del Suelo , Terpenos/farmacología , Terpenos/toxicidadRESUMEN
An anti-mannheimiosis agent, aldsulfin, was isolated from a culture broth of the fungus Lasiodiplodia pseudotheobromae FKI-4499, together with a known compound, lasiodipline C, using bioassay-guided fractionation. Spectroscopic analysis of aldsulfin, using NMR, mass spectrometry, and CD analyses revealed it to be an epithiodiketopiperazine with an unstable and unusual hemithioaminal moiety. Aldsulfin showed antibacterial activity against Mannheimia haemolytica and Pasteurella multocida.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Ascomicetos/metabolismo , Mannheimia haemolytica/efectos de los fármacos , Antibacterianos/aislamiento & purificación , Antibacterianos/metabolismo , Ascomicetos/clasificación , Ascomicetos/genética , Medios de Cultivo/química , Dicetopiperazinas/química , Dicetopiperazinas/farmacología , Evaluación Preclínica de Medicamentos , Fermentación , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Pasteurella multocida/efectos de los fármacosRESUMEN
The targets of antifungal antibiotics in clinical use are more limited than those of antibacterial antibiotics. Therefore, new antifungal antibiotics with different mechanisms of action are desired. In the course of our screening for antifungal antibiotics of microbial origins, new antifungal antibiotics, simplifungin (1) and valsafungins A (2) and B (3), were isolated from cultures of the fungal strains Simplicillium minatense FKI-4981 and Valsaceae sp. FKH-53, respectively. The structures of 1 to 3 including their absolute stereochemistries were elucidated using various spectral analyses including NMR and collision-induced dissociation (CID)-MS/MS as well as chemical approaches including modifications to the Mosher's method. They were structurally related to myriocin. They inhibited the growth of yeast-like and zygomycetous fungi with MICs ranging between 0.125 and 8.0 µg/mL. An examination of their mechanisms of action by the newly established assay using LC-MS revealed that 1 and 2 inhibited serine palmitoyltransferase activity, which is involved in sphingolipid biosynthesis, with IC50 values of 224 and 24 nM, respectively.
Asunto(s)
Antifúngicos/química , Ácidos Grasos Monoinsaturados/química , Antifúngicos/farmacología , Cromatografía Liquida , Ácidos Grasos Monoinsaturados/farmacología , Hongos/efectos de los fármacos , Hongos/crecimiento & desarrollo , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Estereoisomerismo , Espectrometría de Masas en TándemRESUMEN
Two new compounds, designated paraphaeosphaeride D (1) and berkleasmin F (2) together with a previously known compound, berkleasmin A (3), isolated from a culture broth of the fungus Paraphaeosphaeria sp. TR-022, proved to be new circumventors of arbekacin (ABK) resistance in methicillin-resistant Staphylococcus aureus (MRSA). The structures of 1 and 2 were elucidated by spectroscopic analyses, including various NMR experiments. All compounds showed 10-100 times ABK circumvention activities using the paper disc method and reduced the MIC values of ABK against MRSA from 16 µg ml(-1) to 4 µg ml(-1) (fourfold) using the agar dilution method. These new compounds might be promising lead compounds for developing circumventors of ABK resistance in MRSA.
Asunto(s)
Antibacterianos/farmacología , Ascomicetos/metabolismo , Lactamas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pironas/farmacología , Sesquiterpenos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Dibekacina/análogos & derivados , Dibekacina/farmacología , Farmacorresistencia Bacteriana , Lactamas/química , Lactamas/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Pironas/química , Pironas/aislamiento & purificación , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificaciónRESUMEN
Screening for NADH-fumarate reductase inhibitors led to the isolation of a new ukulactone analog, ukulactone C, as a major polyene compound produced by Talaromyces sp. FKI-6713. The structure of the compound was elucidated as a reduced analog of ukulactone A by 1D- and 2D-NMR experiments. Ukulactone C possessed a potent inhibitory activity (IC(50) = 62 nM) against NADH-fumarate reductase of the roundworm Ascaris suum in vitro.
Asunto(s)
Inhibidores Enzimáticos/metabolismo , Lactonas/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Polienos/metabolismo , Talaromyces/metabolismo , Animales , Ascaris suum/enzimología , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Talaromyces/clasificaciónRESUMEN
Two new hydroxycitric acid lactone derivatives named cinatrins D (1) and E (2), and a new γ-lactam, virgaricin B (3), along with a known similar compound, virgaricin (4), were isolated from a fermentation broth of the fungus Virgaria boninensis FKI-4958. The absolute stereo structures of the new compounds were established by a combination of spectroscopic methods and chemical modifications. All three newly discovered compounds possessed weak antibacterial activity.
Asunto(s)
Antibacterianos/farmacología , Ascomicetos/química , Citratos/farmacología , Lactamas/farmacología , Lactonas/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Bacterias/efectos de los fármacos , Citratos/química , Citratos/aislamiento & purificación , Fermentación , Lactamas/química , Lactamas/aislamiento & purificación , Lactonas/química , Lactonas/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Microbiología del SueloRESUMEN
While isolating fungal strains from soil samples, two strains, Talaromyces siamensis FKA-61 and Phomopsis sp. FKA-62, were found to produce a black pigment near the boundary with an adjoining colony on agar plates. Moreover, strain FKA-61 inhibited the growth of strain FKA-62. Co-culture of T. siamensis FKA-61 with Phomopsis sp. FKA-62 resulted in the production of an antifungal agent, BE-31405, which proved active against Phomopsis sp. FKA-62. We screened for fungal genera that have the ability to induce production of antifungal BE-31405. Surprisingly, production of BE-31405 was induced only by co-culturing T. siamensis FKA-61 with a variety of BE-31405-sensitive fungal strains but never with BE-31405-insensitive strains. This is the first report of the induced production of a specific antibiotic active against antibiotic-sensitive fungal strains by co-culturing with them.
Asunto(s)
Antifúngicos/aislamiento & purificación , Hidrocarburos Aromáticos con Puentes/aislamiento & purificación , Hongos/metabolismo , Talaromyces/metabolismo , Técnicas de Cocultivo , Microbiología del SueloAsunto(s)
Antibacterianos/metabolismo , Fusarium/crecimiento & desarrollo , Fusarium/metabolismo , Ácido Penicílico/análogos & derivados , Ácido Penicílico/metabolismo , Talaromyces/crecimiento & desarrollo , Talaromyces/metabolismo , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , ADN de Hongos/química , ADN de Hongos/genética , Fusarium/clasificación , Fusarium/genética , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Molecular , Ácido Penicílico/química , Ácido Penicílico/aislamiento & purificación , Análisis de Secuencia de ADN , Talaromyces/clasificación , Talaromyces/genéticaAsunto(s)
Antihelmínticos/aislamiento & purificación , Descubrimiento de Drogas , Inhibidores Enzimáticos/aislamiento & purificación , Proteínas del Helminto/antagonistas & inhibidores , Neosartorya/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Pironas/aislamiento & purificación , Acetilación , Animales , Antihelmínticos/química , Antihelmínticos/metabolismo , Antihelmínticos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Ascaris suum/enzimología , Bovinos , Pruebas Antimicrobianas de Difusión por Disco , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/crecimiento & desarrollo , Proteínas del Helminto/metabolismo , Japón , Estructura Molecular , Tipificación Molecular , Neosartorya/clasificación , Neosartorya/crecimiento & desarrollo , Neosartorya/aislamiento & purificación , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Pironas/química , Pironas/metabolismo , Pironas/farmacología , Microbiología del Suelo , Estereoisomerismo , Partículas Submitocóndricas/efectos de los fármacos , Partículas Submitocóndricas/enzimologíaRESUMEN
This is the first report describing the improved isolation of common filamentous fungi via a method combining cellulose plate and agar plate system. A cellulose plate is a porous plate made of nanofibrous crystaline cellulose. Isolating fungi from soils using these types of media separately resulted in the number of fungal colonies appearing on cellulose plates being lower than that on agar plates. However, the number of actual fungal species isolated using cellulose plates alone was more or less the same as that found using agar plates. Significantly, the diversity of isolates using a combination of the two media was greater than using each media individually. As a result, numerous new or rare fungal species with potential, including previously proposed new species, were isolated successfully in this way. All fungal colonies, including the Penicillium species, that appeared on the cellulose plate penetrated in potato dextrose were either white or yellow. Cultivation on cellulose plates with added copper ion overcomes the change in coloration, the colonies appearing as they do following cultivation on potato dextrose agar.
Asunto(s)
Agar/química , Celulosa/química , Medios de Cultivo/química , Hongos/aislamiento & purificación , Microbiología del Suelo , Cristalización , Glucosa/química , Nanofibras , Penicillium/aislamiento & purificación , Porosidad , Solanum tuberosum/químicaRESUMEN
Aogacillins A and B, capable of overcoming arbekacin resistance in methicillin-resistant Staphylococcus aureus (MRSA), were isolated from a culture broth of Simplicillium sp. FKI-5985. Their structures were elucidated by NMR spectroscopic studies and ECD analyses. The aogacillins possessed a novel carbon skeleton, including a ß-keto-γ-methyliden-δ-lactone ring connected to a 2-ethyl-6-methylcyclohexane ring by spiro conjugation.
Asunto(s)
Antibacterianos/aislamiento & purificación , Ciclohexanos/aislamiento & purificación , Hypocreales/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Compuestos de Espiro/aislamiento & purificación , Antibacterianos/química , Antibacterianos/farmacología , Ciclohexanos/química , Ciclohexanos/farmacología , Resistencia a la Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Compuestos de Espiro/química , Compuestos de Espiro/farmacologíaRESUMEN
Fifty Pochonia strains were isolated from soil samples collected throughout Japan. Using a combination of micromorphological characters and multigene (SSU, LSU, TEF, RPB1, RPB2) phylogenics, seven taxa were identified, three of which previously were undescribed. In this paper we describe the new species, P. boninensis, and two new varieties, P. chlamydosporia var. ellipsospora and var. spinulospora. They were recovered from Chichi-jima, Aogashima and Okinawa's main island. The three new taxa are distinguished from known species and varieties by conidial morphology. We also report the first finding of P. rubescens from Japan.
Asunto(s)
Hypocreales/clasificación , Microbiología del Suelo , ADN de Hongos/química , ADN de Hongos/genética , Genes Fúngicos/genética , Hifa , Hypocreales/citología , Hypocreales/genética , Hypocreales/aislamiento & purificación , Japón , Tipificación de Secuencias Multilocus , Técnicas de Tipificación Micológica , Filogenia , Esporas FúngicasRESUMEN
Eight new dinapinones, AB1, AB2, AC1, AC2, AD1, AD2, AE1 and AE2, were isolated from the culture broth of Talaromyces pinophilus FKI-3864. The structures of these dinapinones were elucidated by various NMR experiments. All these dinapinones possessed the same biaryl dihydronaphthopyranone skeleton consisting of a heterodimer with one monapinone A and one different monapinone. Dinapinones AB1 and AB2, consisting of monapinones A and B, were atropisomers. Similarly, dinapinones AC1 and AC2, consisting of monapinones A and C, dinapinones AD1 and AD2, consisting of monapinones A and D, and dinapinones AE1 and AE2, consisting of monapinones A and E, were atropisomers. Dinapinone AB2 showed potent inhibition of triacylglycerol (TG) synthesis in intact mammalian cells with an IC50 value of 1.17 µM, whereas the other dinapinones showed weak inhibition of TG synthesis.
Asunto(s)
Cumarinas/farmacología , Talaromyces/metabolismo , Triglicéridos/antagonistas & inhibidores , Animales , Células CHO , Cumarinas/química , Cumarinas/aislamiento & purificación , Cricetinae , Cricetulus , Medios de Cultivo , Fermentación , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estereoisomerismo , Triglicéridos/biosíntesisRESUMEN
Cylindrol A5, a new ascochlorin congener, was isolated along with 14 known compounds from the culture broth of Cylindrocarpon sp. FKI-4602 by solvent extraction, octadecylsilane column chromatography and HPLC. The structure of cylindrol A5 was elucidated by spectral analyses, including NMR. The compound has an ascochlorin skeleton consisting of a resorcin aldehyde and a cyclohexanone moieties. Cylindrol A5 showed moderate antimicrobial activity against Bacillus subtilis, Kocuria rhizophila, Mycobacterium smegmatis and Acholeplasma laidlawii. The biosynthetic pathway to cylindrol A5 was deduced from the 14 isolated metabolites of the fungal strain.
Asunto(s)
Alquenos/aislamiento & purificación , Antibacterianos/aislamiento & purificación , Ascomicetos/metabolismo , Fenoles/aislamiento & purificación , Alquenos/química , Alquenos/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Cromatografía Líquida de Alta Presión , Medios de Cultivo , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Fenoles/química , Fenoles/farmacologíaRESUMEN
An enzyme assay for bacterial undecaprenyl pyrophosphate (UPP) synthase was performed to screen microbial culture broths for inhibitors of UPP synthase. During the course of this screening program, an EtOH extract of a rice culture of Penicillium brasilianum FKI-3368 was found to inhibit UPP synthase activity. From activity-guided purification, a new compound-designated spirohexaline was isolated together with the structurally related and known viridicatumtoxin by ethyl acetate extraction silica gel and octadecylsilane column chromatographies and high-performance liquid chromatography. The structure of spirohexaline was elucidated by spectroscopic analysis, including NMR. Spirohexaline and viridicatumtoxin have a common hexacycline structure produced by fusion of a tetracycline-type ring with a spiro-type ring. They inhibited UPP synthase activity with IC50 values of 9.0 and 4.0 µM, respectively.
Asunto(s)
Transferasas Alquil y Aril/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Micotoxinas/farmacología , Penicillium/metabolismo , Compuestos de Espiro/farmacología , Cromatografía en Gel , Cromatografía Líquida de Alta PresiónRESUMEN
A convenient and efficient method was established for isolating antifungal antibiotic-producing fungi from soil samples. In this method, soil samples were diluted and directly plated in agar medium by the standard fungi-isolating method, and the plates were cultured at 27 °C for 2-3 days to permit the growth of fungal colonies. Then, the suspension of pathogenic Candida albicans in saline (40 µl, 5-10 × 105 CFU ml⻹) was overlaid by spraying on the plates under controlled conditions in the safety cabinet. After 1-day incubation, fungal colonies showing an antagonistic effect with the inhibition zone against sprayed C. albicans were selected. Among 151 isolates, 26 strains were found to reproduce anti-C. albicans activity in liquid medium, yielding a higher selection rate (17.2%) than that (3.1%) by the traditional method. This new method can be applied for isolation of microorganisms (fungi and actinomycetes) that produce antibiotics active against pathogenic microorganisms.
Asunto(s)
Antibacterianos/biosíntesis , Candida albicans/aislamiento & purificación , Candida albicans/metabolismo , Recuento de Colonia Microbiana , Medios de Cultivo , Fermentación , Microbiología del SueloRESUMEN
A new microbial metabolite, cytosporone S (1) was isolated from a fermentation broth of the fungus Trichoderma sp. FKI-6626. Its chemical structure was determined primarily by NMR spectroscopy and mass spectrometry. Compound 1 showed antimicrobial activity against several Gram-positive and Gram-negative bacteria and fungi.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Benzopiranos/aislamiento & purificación , Benzopiranos/farmacología , Hongos/efectos de los fármacos , Trichoderma/química , Antibacterianos/química , Antifúngicos/química , Benzopiranos/química , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad MicrobianaAsunto(s)
Acetiltransferasas/antagonistas & inhibidores , Antibacterianos/farmacología , Dibekacina/análogos & derivados , Inhibidores Enzimáticos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Dibekacina/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Furanos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Verticillium sp. FKI-2679, a soil isolate, was found to produce inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT) in a cell-based assay using ACAT1- and ACAT2-expressing CHO cells. Three new compounds, verticilides A2, A3 and B1, were isolated along with a known compound, verticilide A1, from the fermentation broth of the fungus by solvent extraction, ODS column chromatography, silica gel column chromatography and preparative HPLC. Structure elucidation showed that these compounds were new cyclic depsipeptide. Verticilides A1, A2, A3 and B1 showed a degree of selectivity towards ACAT2, with IC(50)s 8.5-11-fold more potent than observed against ACAT1.