validamycins has been researched along with valienamine* in 6 studies
6 other study(ies) available for validamycins and valienamine
Article | Year |
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A Validamycin Shunt Pathway for Valienamine Synthesis in Engineered
Topics: Binding Sites; Catalytic Domain; Cyclohexenes; Escherichia coli; Escherichia coli Proteins; Hexosamines; Inositol; Kinetics; Molecular Docking Simulation; Mutagenesis, Site-Directed; Streptomyces; Transaminases | 2020 |
De Novo Biosynthesis of β-Valienamine in Engineered Streptomyces hygroscopicus 5008.
The C7N aminocyclitol β-valienamine is a lead compound for the development of new biologically active β-glycosidase inhibitors as chemical chaperone therapeutic agents for lysosomal storage diseases. Its chemical synthesis is challenging due to the presence of multichiral centers in the structure. Herein, we took advantage of a heterogeneous aminotransferase with stereospecificity and designed a novel pathway for producing β-valienamine in Streptomyces hygroscopicus 5008, a validamycin producer. The aminotransferase BtrR from Bacillus circulans was able to convert valienone to β-valienamine with an optical purity of up to >99.9% enantiomeric excess value in vitro. When the aminotransferase gene was introduced into a mutant of S. hygroscopicus 5008 accumulating valienone, 20 mg/L of β-valienamine was produced after 96 h cultivation in shaking flasks. This work provides a powerful alternative for preparing the chiral intermediates for pharmaceutical development. Topics: Biosynthetic Pathways; Chromatography, High Pressure Liquid; Cyclohexenes; Hexosamines; Inositol; Kinetics; Metabolic Engineering; Mutation; Phylogeny; Streptomyces; Transaminases | 2016 |
Genetically engineered production of 1,1'-bis-valienamine and validienamycin in Streptomyces hygroscopicus and their conversion to valienamine.
The antifungal agent validamycin A is an important crop protectant and the source of valienamine, the precursor of the antidiabetic drug voglibose. Inactivation of the valN gene in the validamycin A producer, Streptomyces hygroscopicus subsp. jinggangensis 5008, resulted in a mutant strain that produces new secondary metabolites 1,1'-bis-valienamine and validienamycin. The chemical structures of 1,1'-bis-valienamine and validienamycin were elucidated by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy in conjunction with mass spectrometry and bioconversion employing a glycosyltransferase enzyme, ValG. 1,1'-Bis-valienamine and validienamycin exhibit a moderate antifungal activity against Pellicularia sasakii. Chemical degradation of 1,1'-bis-valienamine using N-bromosuccinimide followed by purification of the products with ion-exchange column chromatography only resulted in valienamine, whereas parallel treatments of validoxylamine A, the aglycon of validamycin A, resulted in an approximately 1:1 mixture of valienamine and validamine, underscoring the advantage of 1,1'-bis-valienamine over validoxylamine A as a commercial source of valienamine. Topics: Antifungal Agents; Cyclohexenes; Fungi; Gene Deletion; Genes, Bacterial; Hexosamines; Inositol; Magnetic Resonance Spectroscopy; Mass Spectrometry; Streptomyces | 2009 |
Preparation of 3-ketovalidoxylamine A C-N lyase substrate: N-p-nitrophenyl-3-ketovalidamine by Stenotrophomonas maltrophilia CCTCC M 204024.
3-Ketovalidoxylamine A C-N lyase is one of three key enzymes in the production of valienamine, which is a potent glucosidase inhibitor from validamycin A. N-p-Nitrophenyl-3-ketovalidamine, used as the substrate of 3-ketovalidoxylamine A C-N lyase, was prepared from N-p-nitrophenylvalidamine with free cells of Stenotrophomonas maltrophilia CCTCC M 204024. The yield and selectivity of N-p-nitrophenyl-3-ketovalidamine from cells were improved by treatment with 10 mM ethylenediaminetetraacetic acid. The optimal pH and temperature for N-p-nitrophenyl-3-ketovalidamine formation was pH 6.0 and 30 degrees C, respectively. N-p-Nitrophenyl-3-ketovalidamine was formed with a yield of 0.68 in the first batch. Topics: Carbon-Nitrogen Lyases; Cyclohexenes; Edetic Acid; Hexosamines; Hydrogen-Ion Concentration; Inositol; Kinetics; Models, Chemical; Molecular Structure; Nitrophenols; Stenotrophomonas; Substrate Specificity; Temperature | 2007 |
Inhibition of porcine small intestinal sucrase by valienamine.
Valienamine, an aminocyclitol, has been isolated from the enzymolysis broth of validamycins. The absolute configuration of valienamine is similar to that of alpha-D-glucose. The inhibitory effect of this amino-sugar analog of alpha-D-glucose, valienamine, on porcine small intestinal sucrase was examined. Valienamine was found to be potent, competitive reversible inhibitor of porcine small intestinal sucrase in vitro with an IC50 value of 1.17 x 10(-3)M. Valienamine also exhibited dose-dependent, instantaneous inhibition of porcine small intestinal sucrase. The inhibition of porcine small intestinal sucrase by valienamine was pH-independent. Topics: Animals; Cyclohexenes; Hexosamines; Hydrogen-Ion Concentration; Inositol; Intestine, Small; Sucrase; Swine | 2005 |
Biosynthesis of the C(7)-cyclitol moiety of acarbose in Actinoplanes species SE50/110. 7-O-phosphorylation of the initial cyclitol precursor leads to proposal of a new biosynthetic pathway.
We have previously demonstrated that the biosynthesis of the C(7)-cyclitol, called valienol (or valienamine), of the alpha-glucosidase inhibitor acarbose starts from the cyclization of sedo-heptulose 7-phosphate to 2-epi-5-epi-valiolone (Stratmann, A., Mahmud, T., Lee, S., Distler, J., Floss, H. G., and Piepersberg, W. (1999) J. Biol. Chem. 274, 10889-10896). Synthesis of the intermediate 2-epi-5-epi-valiolone is catalyzed by the cyclase AcbC encoded in the biosynthetic (acb) gene cluster of Actinoplanes sp. SE50/110. The acbC gene lies in a possible transcription unit, acbKLMNOC, cluster encompassing putative biosynthetic genes for cyclitol conversion. All genes were heterologously expressed in strains of Streptomyces lividans 66 strains 1326, TK23, and TK64. The AcbK protein was identified as the acarbose 7-kinase, which had been described earlier (Drepper, A., and Pape, H. (1996) J. Antibiot. (Tokyo) 49, 664-668). The multistep conversion of 2-epi-5-epi-valiolone to the final cyclitol moiety was studied by testing enzymatic mechanisms such as dehydration, reduction, epimerization, and phosphorylation. Thus, a phosphotransferase activity was identified modifying 2-epi-5-epi-valiolone by ATP-dependent phosphorylation. This activity could be attributed to the AcbM protein by verifying this activity in S. lividans strain TK64/pCW4123M, expressing His-tagged AcbM. The His-tagged AcbM protein was purified and subsequently characterized as a 2-epi-5-epi-valiolone 7-kinase, presumably catalyzing the first enzyme reaction in the biosynthetic route, leading to an activated form of the intermediate 1-epi-valienol. The AcbK protein could not catalyze the same reaction nor convert any of the other C(7)-cyclitol monomers tested. The 2-epi-5-epi-valiolone 7-phosphate was further converted by the AcbO protein to another isomeric and phosphorylated intermediate, which was likely to be the 2-epimer 5-epi-valiolone 7-phosphate. The products of both enzyme reactions were characterized by mass spectrometric methods. The product of the AcbM-catalyzed reaction, 2-epi-5-epi-valiolone 7-phosphate, was purified on a preparative scale and identified by NMR spectroscopy. A biosynthetic pathway for the pseudodisaccharidic acarviosyl moiety of acarbose is proposed on the basis of these data. Topics: Acarbose; Actinobacteria; Adenosine Triphosphate; Amino Acid Sequence; Anti-Bacterial Agents; Catalysis; Chromatography, Thin Layer; Cloning, Molecular; Cyclohexenes; DNA; Electrophoresis, Polyacrylamide Gel; Hexosamines; Inositol; Ions; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Chemical; Molecular Sequence Data; Phosphorylation; Plasmids; Sequence Homology, Amino Acid | 2002 |