A5087565806- Microbial Natural Products and Biosynthesis
- Biochemical and Structural Characterization
- Chemical Synthesis and Analysis
- Genomics and Phylogenetic Studies
- Antimicrobial Peptides and Activities
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Plant biochemistry and biosynthesis
- Toxin Mechanisms and Immunotoxins
- RNA and protein synthesis mechanisms
- Microbial Metabolism and Applications
- vaccines and immunoinformatics approaches
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Computational Drug Discovery Methods
- Protein Hydrolysis and Bioactive Peptides
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Probiotics and Fermented Foods
- Marine Sponges and Natural Products
- Nicotinic Acetylcholine Receptors Study
- Enzyme Structure and Function
Novartis (United States)
2023-2024
Novartis (Switzerland)
2024
University of Illinois Urbana-Champaign
2017-2019
Urbana University
2018
Center for Genomic Science
2018
Many antibiotics, chemotherapeutics, crop protection agents and food preservatives originate from molecules produced by bacteria, fungi or plants. In recent years, genome mining methodologies have been widely adopted to identify characterize the biosynthetic gene clusters encoding production of such compounds. Since 2011, 'antibiotics secondary metabolite analysis shell-antiSMASH' has assisted researchers in efficiently performing this, both as a web server standalone tool. Here, we present...
Antimicrobial resistance is a leading mortality factor worldwide. Here, we report the discovery of clovibactin, an antibiotic isolated from uncultured soil bacteria. Clovibactin efficiently kills drug-resistant Gram-positive bacterial pathogens without detectable resistance. Using biochemical assays, solid-state nuclear magnetic resonance, and atomic force microscopy, dissect its mode action. blocks cell wall synthesis by targeting pyrophosphate multiple essential peptidoglycan precursors...
Recently developed bioinformatic tools have bolstered the discovery of ribosomally synthesized and post-translationally modified peptides (RiPPs). Using an improved version Rapid ORF Description Evaluation Online (RODEO 2.0), a biosynthetic gene cluster mining algorithm, we bioinformatically mapped sactipeptide RiPP class via radical S-adenosylmethionine (SAM) enzymes that form characteristic sactionine (sulfur-to-α carbon) cross-links between cysteine acceptor residues. Hundreds new...
Thiopeptides are members of the ribosomally synthesized and post-translationally modified peptide family natural products. Most characterized thiopeptides display nanomolar potency toward Gram-positive bacteria by blocking protein translation with several being produced at industrial scale for veterinary livestock applications. Employing our custom bioinformatics program, RODEO, we expand thiopeptide products a factor four. This effort revealed many new biosynthetic gene clusters predicted...
Substrate binding assays, <italic>in vitro</italic> proteolytic processing and heterologous lasso peptide production were used to investigate the roles of conserved precursor residues during paeninodin maturation.
The bottromycins belong to the ribosomally synthesized and posttranslationally modified peptide (RiPP) family of natural products. Bottromycins exhibit unique structural features, including a hallmark macrolactamidine ring thiazole heterocycle for which divergent members YcaO superfamily have been biosynthetically implicated. Here we report in vitro reconstitution two proteins, BmbD BmbE, responsible ATP-dependent cyclodehydration reactions that yield thiazoline-...
Antimicrobial resistance is a leading mortality factor worldwide. Here we report the discovery of clovibactin, new antibiotic, isolated from uncultured soil bacteria. Clovibactin efficiently kills drug-resistant bacterial pathogens without detectable resistance. Using biochemical assays, solid-state NMR, and atomic force microscopy, dissect its mode action. blocks cell wall synthesis by targeting pyrophosphate multiple essential peptidoglycan precursors (C 55 PP, Lipid II, WTA ). uses an...
Abstract Many organisms contain head‐to‐head isoprenoid synthases; we investigated three such types of enzymes from the pathogens Neisseria meningitidis , gonorrhoeae and Enterococcus hirae . The E. enzyme was found to produce dehydrosqualene, solved an inhibitor‐bound structure that revealed a fold similar CrtM Staphylococcus aureus In contrast, homologous proteins spp. carried out only first half reaction, yielding presqualene diphosphate (PSPP). Based on product analyses, bioinformatics,...
Abstract Voltage-gated sodium (Nav) channels sense membrane potential and drive cellular electrical activity. Numerous protein toxins have been identified that modulate Nav gating, structures of in complex with these helped elucidate the molecular mechanisms voltage-dependent channel gating. The deathstalker scorpion α-toxin LqhαIT exerts a strong action prolonging effect on channels. Biochemical studies show features functionally essential epitope at its C-terminus is not shared related...
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Knotted peptides present a wealth of structurally diverse, biologically active molecules, with the inhibitor cystine knot/knottin class among most ecologically common ones. Many these natural products interact extracellular targets such as voltage-gated ion channels exquisite selectivity and potency, making them intriguing therapeutic modalities. Such compounds are often produced in low concentrations by intractable organisms, structural biological characterization challenging, which is...
ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to “Bioinformatic Mapping of Radical S-Adenosylmethionine-Dependent Ribosomally Synthesized and Post-Translationally Modified Peptides Identifies New Cα, Cβ, Cγ-Linked Thioether-Containing Peptides”Graham A. HudsonGraham HudsonMore by Graham Hudson, Brandon J. BurkhartBrandon BurkhartMore Burkhart, Adam DiCaprioAdam DiCaprioMore DiCapriohttps://orcid.org/0000-0001-9880-4493,...