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Systems metabolic engineering of the primary and secondary metabolism of Streptomyces albidoflavus enhances production of the reverse antibiotic nybomycin against multi-resistant Staphylococcus aureus.
Metab Eng
January 2024
Institute of Systems Biotechnology, Saarland University, Saarbrücken, Germany. Electronic address:
Nybomycin is an antibiotic compound with proven activity against multi-resistant Staphylococcus aureus, making it an interesting candidate for combating these globally threatening pathogens. For exploring its potential, sufficient amounts of nybomycin and its derivatives must be synthetized to fully study its effectiveness, safety profile, and clinical applications. As native isolates only accumulate low amounts of the compound, superior producers are needed.
View Article and Find Full Text PDFNybomycin inhibits both types of DNA gyrase - fluoroquinolone-sensitive and fluoroquinolone-resistant.
Antimicrob Agents Chemother
May 2023
Department of Chemistry, Faculty of Bioengineering and Bioinformatics and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.
Bacterial type II topoisomerases, DNA gyrase and topoisomerase IV, are targets of many antibiotics including fluoroquinolones (FQs). Unfortunately, a number of bacterial species easily acquire resistance to FQs by mutations in either DNA gyrase or topoisomerase IV genes. The emergence of resistant pathogenic strains is a global problem in healthcare, therefore, identifying alternative pathways to thwart their persistence is the current frontier in drug discovery.
View Article and Find Full Text PDFBenzanthric Acid, a Novel Metabolite From Del14 Expressing the Nybomycin Gene Cluster.
Front Chem
January 2020
Pharmaceutical Biotechnology, University of Saarland, Saarbrücken, Germany.
Streptomycetes constitute a diverse bacterial group able to produce a wide variety of secondary metabolites with potential applications in the pharmacy industry. However, the genes responsible for the biosynthesis of these compounds are very frequently inactive or expressed at very low levels under standard laboratory cultivation conditions. Therefore, the activation or upregulation of secondary metabolite biosynthesis genes is a crucial step for the discovery of new bioactive natural products.
View Article and Find Full Text PDFStructure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated .
J Nat Prod
December 2019
Markey Cancer Center, Department of Pharmacology and Nutritional Sciences, College of Medicine , University of Kentucky, Lexington , Kentucky 40536 , United States.
We report the isolation and characterization of three new nybomycins (nybomycins B-D, -) and six known compounds (nybomycin, ; deoxynyboquinone, ; α-rubromycin, ; β-rubromycin, ; γ-rubromycin, ; and [2α(1,3),4β]-2-(1,3-pentadienyl)-4-piperidinol, ) from the Rock Creek (McCreary County, KY) underground coal mine acid reclamation site isolate sp. AD-3-6. Nybomycin D () and deoxynyboquinone () displayed moderate () to potent () cancer cell line cytotoxicity and displayed weak to moderate anti-Gram-(+) bacterial activity, whereas rubromycins - displayed little to no cancer cell line cytotoxicity but moderate to potent anti-Gram-(+) bacterial and antifungal activity.
View Article and Find Full Text PDFSynthetic studies on the reverse antibiotic natural products, the nybomycins.
Medchemcomm
August 2019
Department of Chemistry , Imperial College London, Molecular Sciences Research Hub , White City Campus, Wood Lane , London , W12 OBZ , UK . Email:
Antimicrobial resistance (AMR) is a serious issue that could have severe consequences if steps are not taken. The nybomycin natural products have the potential to extend the clinical efficacy of the marketed fluoroquinolone class of antibiotics through a 'reverse antibiotic' approach. However, only very limited structure-activity relationships are known for these fascinating compounds, in part due to challenges with their synthesis.
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