Spiropiperidine naphthyridinone inhibitors of Staphylococcus aureus and Escherichia coli FabI have been prepared. Compounds 14a and 14c were identified as having sub-nanomolar E. coli FabI activity and are among the most potent FabI inhibitors yet described. The structural model of 14a bound to E. coli FabI is shown.
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http://dx.doi.org/10.1016/j.bmcl.2009.07.129 | DOI Listing |
BMC Microbiol
December 2024
Guangdong Provincial Key Laboratory for the Development Biology and Environmental Adaptation of Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
Background: Sinorhizobium meliloti is noted for its exceptional capacity to produce unsaturated fatty acids (UFAs). Earlier studies have indicated that S. meliloti primarily employs the FabA-FabB pathway for UFA synthesis, however, the mechanisms remain elusive.
View Article and Find Full Text PDFNat Commun
October 2024
Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.
All free-living microorganisms homeostatically maintain the fluidity of their membranes by adapting lipid composition to environmental temperatures. Here, we quantify enzymes and metabolic intermediates of the Escherichia coli fatty acid and phospholipid synthesis pathways, to describe how this organism measures temperature and restores optimal membrane fluidity within a single generation after a temperature shock. A first element of this regulatory system is a temperature-sensitive metabolic valve that allocates flux between the saturated and unsaturated fatty acid synthesis pathways via the branchpoint enzymes FabI and FabB.
View Article and Find Full Text PDFPhytomedicine
July 2024
Center of Infectious Diseases and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:
Background: The increase in antimicrobial resistance leads to complications in treatments, prolonged hospitalization, and increased mortality. Glabridin (GLA) is a hydroxyisoflavan from Glycyrrhiza glabra L. that exhibits multiple pharmacological activities.
View Article and Find Full Text PDFJ Chem Inf Model
May 2024
Department of Biomedical Engineering, Wroclaw University of Science and Technology, Wroclaw 50-370, Poland.
Membranes─cells' essential scaffolds─are valid molecular targets for substances with an antimicrobial effect. While certain substances, such as octenidine, have been developed to target membranes for antimicrobial purposes, the recently reported molecule, fabimycin (F2B)─a novel agent targeting drug-resistant Gram-negative bacteria─has not received adequate attention regarding its activity on membranes in the literature. The following study aims to investigate the effects of F2B on different bacterial membrane models, including simple planar bilayers and more complex bilayer systems that mimic the shell equipped with double inner and outer bilayers.
View Article and Find Full Text PDFBiomolecules
April 2024
Research Center of Biotechnology, Russian Academy of Sciences, 33, bld. 2. Leninsky Ave., Moscow 119071, Russia.
Inverted fatty acid β-oxidation represents a versatile biochemical platform for biosynthesis by the engineered microbial strains of numerous value-added chemicals from convenient and abundant renewable carbon sources, including biomass-derived sugars. Although, in recent years, significant progress has been made in the production through this pathway of n-alcohols, 1,3-diols, and carboxylic acids and its 2,3-unsaturated derivatives, the potential of the pathway for the biosynthesis of 3-hydroxycarboxylic acids remained almost undisclosed. In this study, we demonstrate the microaerobic production of even-chain-length C4-C8 3-hydroxycarboxylic acids from glucose through the inverted fatty acid β-oxidation by engineered strains.
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