9 research outputs found

    Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis

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    Additional file 3 : Figure S2. HPLC analysis of milbemycins produced from S. avermitilis mutant strains and authentic standard milbemycins

    Cyclodimerization of Mohangamide A by Thioesterase Domain Is Directed by Substrates

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    Mohangamide A is a pseudo-dimeric nonribosomal peptide biosynthesized along with its monomer, WS9326A, and is expected to be formed by the head-to-tail cyclodimerization of linear WS9326A and another identical peptide chain with a different acyl side chain. In vitro experiments with the N-acetylcysteamine thioesters of the corresponding monomeric intermediates and thioesterase domains of Streptomyces sp. SNMSS and S. calvus showed that this cyclodimerization reaction is directed by the substrate structures and occurs only with both linear intermediates.N

    Characterization of the Two Methylation Steps Involved in the Biosynthesis of Mycinose in Tylosin

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    The <i>S</i>-adenosyl-l-methionine-dependent <i>O</i>-methyltransferases TylE and TylF catalyze the last two methylation reactions in the tylosin biosynthetic pathway of <i>Streptomyces fradiae</i>. It has long been known that the TylE-catalyzed C2‴-<i>O</i>-methylation of the 6-deoxy-d-allose bound to demethylmacrocin or demethyllactenocin precedes the TylF-catalyzed C3‴-<i>O</i>-methylation of the d-javose (C2‴-<i>O</i>-methylated 6-deoxy-d-allose) attached to macrocin or lactenocin. This study reveals the unexpected substrate promiscuity of TylE and TylF responsible for the biosynthesis of d-mycinose (C3‴-<i>O</i>-methylated d-javose) in tylosin through the identification of a new minor intermediate 2‴-<i>O</i>-demethyldesmycosin (<b>2</b>; 3‴-methyl-demethyllactenocin), which lacks a 2‴-<i>O</i>-methyl group on the mycinose moiety of desmycosin, along with 2‴-<i>O</i>-demethyltylosin (<b>1</b>; 3‴-methyl-demethylmacrocin) that was previously detected from the <i>S. fradiae</i> mutant containing a mutation in the <i>tylE</i> gene. These results unveil the unique substrate flexibility of TylE and TylF and demonstrate their potential for the engineered biosynthesis of novel glycosylated macrolide derivatives

    One-Pot Combinatorial Biosynthesis of Glycosylated Anthracyclines by Cocultivation of <i>Streptomyces</i> Strains Producing Aglycones and Nucleotide Deoxysugars

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    Anthracyclines, such as doxorubicin, are effective anticancer drugs composed of a tetracyclic polyketide aglycone and one or more deoxysugar moieties, which play a critical role in their biological activity. A facile one-pot combinatorial biosynthetic system was developed for the generation of a range of glycosylated derivatives of anthracyclines. Cocultivation of <i>Streptomyces venezuelae</i> mutants producing two anthracycline aglycones with eight different nucleotide deoxysugar-producing <i>S. venezuelae</i> mutants that coexpress a substrate-flexible glycosyltransferase led to the generation of 16 aklavinone or ε-rhodomycinone glycosides containing diverse deoxysugar moieties, seven of which are new. This demonstrates the potential of the one-pot combinatorial biosynthetic system based on cocultivation as a facile biological tool capable of combining diverse aglycones and deoxysugars to generate structurally diverse polyketides carrying engineered sugars for drug discovery and development

    Nyuzenamide C, an Antiangiogenic Epoxy Cinnamic Acid-Containing Bicyclic Peptide from a Riverine Streptomyces sp.

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    A new nonribosomal peptide, nyuzenamide C (1), was discovered from riverine sediment-derived Streptomyces sp. DM14. Comprehensive analysis of the spectroscopic data of nyuzenamide C (1) revealed that 1 has a bicyclic backbone composed of six common amino acid residues (Asn, Leu, Pro, Gly, Val, and Thr) and four nonproteinogenic amino acid units, including hydroxyglycine, beta-hydroxyphenylalanine, p-hydroxyphenylglycine, and 3,beta-dihydroxytyrosine, along with 1,2-epoxypropyl cinnamic acid. The absolute configuration of 1 was proposed by J-based configuration analysis, the advanced Marfey&apos;s method, quantum mechanics-based DP4 calculations, and bioinformatic analysis of its nonribosomal peptide synthetase biosynthetic gene cluster. Nyuzenamide C (1) displayed antiangiogenic activity in human umbilical vein endothelial cells and induced quinone reductase in murine Hepa-1c1c7 cells.N

    Flexible supercapacitor fabrication by room temperature rapid laser processing of roll-to-roll printed metal nanoparticle ink for wearable electronics application

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    We introduce a rapid and low-temperature laser annealing process of roll-to-roll (R2R) printed metal nanoparticle (NP) ink on a polymer substrate as an alternative to the conventional thermal annealing process using expensive and time consuming lengthy furnace. Due to the confined heating induced by the focused laser, R2R printed Ag NP film is selectively turned into a continuous conductive film without heating the whole substrate. As a result, the damage on the underlying polymer substrate, as well as the processing time required for the annealing, is significantly reduced by the laser annealing compared to the conventional thermal annealing. The resultant laser annealed Ag NP film also exhibits superior electrical and mechanical properties in comparison to the thermal annealed sample. The laser annealed Ag NP film is further applied to the flexible supercapacitor as the current collector in order to confirm the excellence of laser annealed Ag NP film in the fabrication of practical devices. (C) 2013 Elsevier B.V. All rights reserved.N
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