Discovery of an Iron-Regulated Citrate Synthase in Staphylococcus aureus

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Highlights? Staphylococcus aureus SbnG is discovered to be an iron-regulated citrate synthase ? SbnG provides citrate for synthesis of the citrate siderophore staphyloferrin B ? Staphyloferrin B can be synthesized in vitro using purified enzymes ? SbnG inhibitors identified     

Structures of Cyanobactin Maturation Enzymes Define a Family of Transamidating Proteases

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Highlights? Boundaries for cyanobactin maturation protease domains determined ? Structures of protease domains for cyanobactin maturation enzymes determined ? Additional structural motif in PatG assists in cyclizing transamidation ? Rational mutagenesis of active site leads to altered catalytic profiles for PatG     

Deglycosylation as a Mechanism of Inducible Antibiotic Resistance Revealed Using a Global Relational Tree for One-Component Regulators

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Highlights? Phylogenomics can be used to predict cognate ligands for TetR-family regulators ? KijR (SCO7719) regulates kijX (SCO7720) in response to the antibiotic kijanimicin ? kijX encodes a kijanimicin-resistance determinant ? KijX is a glycosyl hydrolase and inactivates kijanimicin through deglycosylation     

Synthetic Evolving Systems that Implement a User-Specified Genetic Code of Arbitrary Design

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Highlights? Populations of replicating RNAs were constructed by encoded combinatorial chemistry ? The RNAs evolve based on a heritable genotype and corresponding catalytic phenotype ? Genotype and phenotype are related by a user-specified genetic code ? The evolved enzymes included both highly active catalysts and molecular parasites     

Characterization of a Silent Azaphilone Gene Cluster from Aspergillus niger ATCC 1015 Reveals a Hydroxylation-Mediated Pyran-Ring Formation

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Highlights? Discovery of an azaphilone pathway in Aspergillus niger ? Six azaphilone compounds were isolated and characterized ? The biosynthesis involves convergent actions of an HR-PKS and an NR-PKS ? Hydroxylation by a monooxygenase promotes pyran-ring formation     

Validation of the Proteasome as a Therapeutic Target in Plasmodium Using an Epoxyketone Inhibitor with Parasite-Specific Toxicity

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Highlights? Purification of Plasmodium proteasomes and labeling with an activity-based probe ? Identification of an epoxyketone-based inhibitor with parasite-specific toxicity ? Demonstration that Plasmodium is sensitive to partial inhibition of its proteasome ? Determination of key parameters for selective parasite killing with proteasome inhibitors     

Recycling of Informational Units Leads to Selection of Replicators in a Prebiotic Soup

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Highlights? Recycling of genetic material is important for the origins of life ? Simulation studies show recycling leads to the selection of genotypes from a pool ? Recycling can lead to the sudden emergence of a high-fitness RNA genotype ? Experimental studies with the Azoarcus ribozyme show fragment recycling     

Characterization of a Fungal Thioesterase Having Claisen Cyclase and Deacetylase Activities in Melanin Biosynthesis

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Highlights? Revised C. lagenarium Pks1 coding sequence enabling in vitro analysis ? Clarified third fungal route to dihydroxynaphthalene melanin ? Revealed thioesterase-catalyzed tandem Claisen cyclization and deacetylation ? Lid swap chimera illuminate features necessary for C-C bond making and breaking     

Flux through Trehalose Synthase Flows from Trehalose to the Alpha Anomer of Maltose in Mycobacteria

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Highlights? Flux through trehalose synthase (TreS) in mycobacteria is from trehalose to maltose ? The appropriate α anomer is formed by TreS for maltose kinase of the GlgE pathway ? The specificity of TreS for α-maltose is retained with deoxyfluoro analogs ? TreS supports cytosolic/capsular α-glucan but not trehalose mycolate biosynthesis     

Orthogonal Ubiquitin Transfer through Engineered E1-E2 Cascades for Protein Ubiquitination

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Highlights? Orthogonal ubiquitin (UB) transfer pathway to synthesize specific UB-E2 conjugates ? Phage display to engineer UB-E1 and UB-E2 interactions ? Engineered xUB-xE1 and xE1-xE2 pairs with no cross-reactivities with native enzymes     

A Bacterial Source for Mollusk Pyrone Polyketides

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Highlights? Symbiotic bacteria synthesize compounds found in mollusks ? Physically defended mollusks provide a source for bioactive metabolite discovery ? A type of pyrone polyketide pathway described ? Nocardiopsis strains may be widespread, casually associated symbionts of inveterbrates     

Interplay between the Ribosomal Tunnel,Nascent Chain,and Macrolides Influences Drug Inhibition

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Highlights? Macrolides exhibit nascent polypeptide chain–dependent inhibition ? Peptides can form specific interactions with the ribosomal tunnel ? A covalent bond between tylosin and the ribosome is necessary for inhibitory activity     

Cloning,Heterologous Expression,and Characterization of the Gene Cluster Required for Gougerotin Biosynthesis

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Highlights? The complete gougerotin biosynthetic gene cluster is cloned ? Heterologous production of gougerotin is accomplished in S. coelicolor M1146 ? Biosynthetic pathway is proposed based on bioinformatics, genetic, and chemical analyses ? Preliminary data support an uncommon enzymatic reaction for peptide bond formation     

Elucidation of Piericidin A1 biosynthetic locus revealed a thioesterase-dependent mechanism of α-pyridone ring formation

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Highlights? Genome scanning revealed a pathway for α-pyridone antibiotics in bacteria ? Gene replacements verified pieA, C, D are involved in piericidin A1 biosynthesis ? In vitro characterization showed that PieA-TE mediates polyketide hydrolysis ? Biosynthesis of α-pyridone via hydrolysis followed by amidation and cyclization     

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Potent Immunoresolvents

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Highlights? RvD3 accumulates in late inflammation resolution ? Aspirin triggers biosynthesis of RvD3 17R-epimer (AT-RvD3) that is proresolving ? Complete stereochemistry of RvD3 and AT-RvD3 are established ? RvD3 and AT-RvD3 govern leukocyte functions and local inflammatory responses     

Chemical perturbation of secondary metabolism demonstrates important links to primary metabolism

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Highlights? A chemical screen recapitulates all genetic phenotypes in S. coelicolor ? 19 compounds remodel secondary metabolism in Streptomyces coelicolor ? Partial inhibition of fatty acid synthesis remodels secondary metabolite production     

Biosynthesis of the Respiratory Toxin Bongkrekic Acid in the Pathogenic Bacterium Burkholderia gladioli

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Highlights? Molecular basis for the biosynthesis of a fatal food toxin revealed ? Functional genetics by λ Red recombination in the pathogen Burkholderia gladioli ? Stereochemistry of modular bongkrekic acid PKS decoded ? β-Branching and six-electron methyl oxidation lead to tricarboxylic fatty acid     

Reconstitution of Nucleosome Demethylation and Catalytic Properties of a Jumonji Histone Demethylase

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Highlights? Catalytic domain of JMJD2A (cJMJD2A) removes methyl marks in a distributive manner ? Homogeneously methylated nucleosomes were used as substrates ? Quantitative assay for nucleosome demethylation has been developed     

Terpendole E,a Kinesin Eg5 Inhibitor,Is a Key Biosynthetic Intermediate of Indole-Diterpenes in the Producing Fungus Chaunopycnis alba

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Highlights? The terpendole biosynthetic gene cluster was isolated ? Terpendole E is a key biosynthetic intermediate of indole-diterpenes ? Terpendole E was overproduced by gene knockout of the bispecific enzyme TerP ? Indole-diterpene biosynthetic pathways can be classified into two groups     

A Designed Inhibitor of a CLC Antiporter Blocks Function through a Unique Binding Mode

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Highlights? OADS is a known small-molecule inhibitor of a CLC antiporter ? OADS specifically inhibits the ClC-ec1 antiporter but not the ClC-1 channel ? Photoaffinity labeling and mass spectrometry have localized OADS binding to two discrete sites ? The unique binding mode and lipid dependence of OADS suggest potential mechanisms of action