Improvement of the antimicrobial potency, pharmacokinetic and pharmacodynamic properties of albicidin by incorporation of nitrogen atoms.

The worrisome development and spread of multidrug-resistant bacteria demands new antibacterial agents with strong bioactivities particularly against Gram-negative bacteria. Albicidins were recently structurally characterized as highly active antibacterial natural products from the bacterium . Albicidin, which effectively targets the bacterial DNA-gyrase, is a lipophilic hexapeptide mostly consisting of amino benzoic acid units and only one α-amino acid.

How Many O-Donor Groups in Enterobactin Does It Take to Bind a Metal Cation?

The E. coli siderophore enterobactin, the strongest Fe chelator known to date, forms hexacoordinate complexes with Si , Ge , and Ti . Synthetic protocols have been developed to prepare non-symmetric enterobactin analogues with varying denticities.

Molecular insights into antibiotic resistance - how a binding protein traps albicidin.

The worldwide emergence of antibiotic resistance poses a serious threat to human health. A molecular understanding of resistance strategies employed by bacteria is obligatory to generate less-susceptible antibiotics. Albicidin is a highly potent antibacterial compound synthesized by the plant-pathogenic bacterium Xanthomonas albilineans.

Total Synthesis and Biological Assessment of Novel Albicidins Discovered by Mass Spectrometric Networking.

Natural products represent an important source of potential novel antimicrobial drug leads. Low production by microorganisms in cell culture often delays the structural elucidation or even prevents a timely discovery. Starting from the anti-Gram-negative antibacterial compound albicidin produced by Xanthomonas albilineans, we describe a bioactivity-guided approach combined with non-targeted tandem mass spectrometry and spectral (molecular) networking for the discovery of novel antimicrobial compounds.

Synthesis and Antimicrobial Activity of Albicidin Derivatives with Variations of the Central Cyanoalanine Building Block.

To investigate the pharmacophore regions of the antibiotic albicidin, derivatives with variations on the central amino acid were synthesized. Charged as well as uncharged residues were chosen to explore the influence of charge, chirality, and steric bulk. The bioactivity of the newly synthesized derivatives was determined by a microdilution technique to obtain minimum inhibitory concentrations (MIC) values.

The O-Carbamoyl-Transferase Alb15 Is Responsible for the Modification of Albicidin.

Albicidin is a potent antibiotic and phytotoxin produced by Xanthomonas albilineans which targets the plant and bacterial DNA gyrase. We now report on a new albicidin derivative which is carbamoylated at the N-terminal coumaric acid by the action of the ATP-dependent O-carbamoyltransferase Alb15, present in the albicidin (alb) gene cluster. Carbamoyl-albicidin was characterized by tandem mass spectrometry from cultures of a Xanthomonas overproducer strain and the gene function confirmed by gene inactivation of alb15 in X.

ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT.

The objective of this study was to establish the role of apoA-IV, ABCA1, and LCAT in the biogenesis of apoA-IV-containing HDL (HDL-A-IV) using different mouse models. Adenovirus-mediated gene transfer of apoA-IV in apoA-I(-/-) mice did not change plasma lipid levels. ApoA-IV floated in the HDL2/HDL3 region, promoted the formation of spherical HDL particles as determined by electron microscopy, and generated mostly α- and a few pre-β-like HDL subpopulations.