RESUMEN
Cytochrome P450sca-2 from Streptomyces carbophilus catalyzes the hydroxylation of ML-236B sodium salt to pravastatin sodium, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase. HMG-CoA reductase is a key enzyme in cholesterol biosynthesis. Crystals of the protein were obtained by the vapour-diffusion method, using ammonium sulfate as a precipitant. The crystals belong to the trigonal space group P3121 (or its enantiomorph, P3221) with unit-cell dimensions a = 103.5, c = 79.8 A. Assuming the presence of one molecule in the asymmetric unit, the calculated value of Vm is 2.68 A3 Da-1. A native data set was collected to a resolution of 2.2 A.
Asunto(s)
Sistema Enzimático del Citocromo P-450/química , Inhibidores de Hidroximetilglutaril-CoA Reductasas/metabolismo , Oxigenasas de Función Mixta/química , Pravastatina/biosíntesis , Streptomyces/enzimología , Cristalización , Cristalografía por Rayos X , Sistema Enzimático del Citocromo P-450/aislamiento & purificación , Sistema Enzimático del Citocromo P-450/metabolismo , Oxigenasas de Función Mixta/aislamiento & purificación , Oxigenasas de Función Mixta/metabolismo , Conformación Proteica , Difracción de Rayos XRESUMEN
A novel acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A has been isolated from the fermentation broth of Stachybotrys bisbyi SANK 17777. The molecular formula, physicochemical properties, NMR spectroscopic analysis and X-ray crystallographic analysis revealed that this compound was a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent. It inhibited ACAT activity in an enzyme assay using rat liver microsomes with an IC50 value of 1.7 microM. However, it showed about 10-fold less potent inhibitory effect on plasma lecithin cholesterol acyltransferase (LCAT) than on ACAT. In addition, it inhibited in vivo cholesterol absorption in rats by 50% at 75 mg/kg.
Asunto(s)
Benzoquinonas/aislamiento & purificación , Esterol O-Aciltransferasa/antagonistas & inhibidores , Animales , Antinematodos , Benzoquinonas/química , Benzoquinonas/farmacología , Fermentación , Masculino , Microsomas Hepáticos/efectos de los fármacos , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Stachybotrys , EstereoisomerismoRESUMEN
Novel heparanse inhibitors, A72363 A-1, A-2, and C, were isolated from the culture filtrate of Streptomyces nobilis SANK 60192 by column chromatography on various resinous adsorbents, followed by preparative anion exchange HPLC. Spectroscopic studies revealed that they are diastereomers of siastatin B, a neuraminidase inhibitor.
Asunto(s)
Inhibidores Enzimáticos/aislamiento & purificación , Fermentación , Glucuronidasa , Glicósido Hidrolasas/antagonistas & inhibidores , Piperidinas/aislamiento & purificación , Streptomyces/metabolismo , Inhibidores Enzimáticos/química , Piperidinas/química , Streptomyces/clasificaciónAsunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/química , Antibacterianos/farmacología , Lactamas , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Mupirocina/análogos & derivados , Mupirocina/química , Mupirocina/aislamiento & purificación , Mupirocina/farmacología , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Thiomarinol, an antimicrobial antibiotic, was isolated from the culture broth of a marine bacterium, Alteromonas rava sp. nov. SANK 73390. Its structure was deduced as a hybrid composed of a pseudomonic acid analogue and holothin by NMR spectral analysis and chemical degradation. Antimicrobial activity against Gram-positive and Gram-negative bacteria of thiomarinol was stronger than both of pseudomonic acids and pyrrothine antibiotics.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Bacterias Aerobias Gramnegativas/química , Mupirocina/análogos & derivados , Antibacterianos/química , Fenómenos Químicos , Química Física , Fermentación , Bacterias Aerobias Gramnegativas/metabolismo , Lactamas , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Mupirocina/química , Mupirocina/aislamiento & purificación , Mupirocina/farmacologíaRESUMEN
New inositol-1,4,5-trisphosphate (InsP3) agonists, adenophostins A(1) and B(2), were isolated from the culture broth of Penicillium brevicompactum SANK 11991 and SANK 12177. Its structures were related to adenine nucleotides. The agonistic activity of adenophostins A or B for binding to the InsP3 receptor was higher than InsP3 itself.
Asunto(s)
Adenina/análogos & derivados , Adenosina/análogos & derivados , Canales de Calcio/efectos de los fármacos , Inositol 1,4,5-Trifosfato/metabolismo , Penicillium/química , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Adenosina/química , Adenosina/aislamiento & purificación , Adenosina/metabolismo , Animales , Canales de Calcio/metabolismo , Cromatografía Líquida de Alta Presión , Fermentación , Receptores de Inositol 1,4,5-Trifosfato , Ratones , Receptores Citoplasmáticos y Nucleares/metabolismoRESUMEN
Three metabolites were isolated from the culture broth of an actinomycete strain identified as Streptomyces platensis SANK 60191, that induce the production of colony-stimulating factors (CSFs) by stromal cell line KM-102 at ED50 concentrations from 40 to 200 ng/ml. The compounds induced quantities of granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) comparable to those induced by interleukin-1, a strong CSF inducer. These metabolites were called leustroducsins (A, B and C) and were later found to be structurally related to phoslactomycins. This is the first report of CSF inducing activity by members of the phoslactomycin class.
Asunto(s)
Médula Ósea/efectos de los fármacos , Ácidos Grasos Insaturados/aislamiento & purificación , Factor Estimulante de Colonias de Granulocitos/biosíntesis , Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Streptomyces/química , Antifúngicos/farmacología , Médula Ósea/metabolismo , Línea Celular , Ácidos Grasos Insaturados/química , Ácidos Grasos Insaturados/farmacología , Fermentación , Humanos , Lactonas/química , Lactonas/aislamiento & purificación , Lactonas/farmacología , Compuestos Organofosforados/química , Compuestos Organofosforados/aislamiento & purificación , Compuestos Organofosforados/farmacología , Pironas , Relación Estructura-ActividadRESUMEN
A strain of actinomycetes identified as Pseudonocardia compacta subsp. helvetica produced new glycopeptide antibiotics, helvecardins A and B. They were isolated from culture broth mainly by affinity chromatography of D-alanyl-D-alanine and preparative HPLC. The physico-chemical properties of helvecardins A and B showed that they resemble each other. Though helvecardin A was structurally related to beta-avoparcin, it clearly differed in the presence of an O-methyl moiety in its NMR spectrum.