2018年10月31日 · Whole-genome sequencing of K. pneumoniae JWM0012 and JWM0013 revealed the presence of mutations in lpxC and fabZ (encoding LpxC V37G /FabZ R121L and LpxC V37G /FabZ F51L, respectively) along with additional mutations (see Table S1 in the supplemental material).

2023年1月16日 · Here, we perform deep mutational scanning on three essential E. coli proteins (FabZ, LpxC and MurA) involved in cell envelope synthesis using high-throughput CRISPR genome editing, and study the...

2023年4月15日 · LpxC and FabZ encoded by two open reading frames were explored for differences in their amino acid sequence. FabZ catalyzes the dehydration of R-3-hydroxymyristoyl-ACP and represents a branch point of acyl …

In this report, we describe the in vitro and in vivo characterization of novel inhibitors of LpxC, an enzyme whose activity is required for proper lipid A biosynthesis, and demonstrate that our lead compound has the requisite attributes to warrant further consideration as a novel antibiotic.

These observations suggest that in fabZ mutants, the mechanism of resistance to LpxC inhibition is restoration of the balance between LPS synthesis and synthesis of phospholipids, reducing flux through both pathways while maintaining the permeability barrier of the outer membrane.

2021年11月26日 · TP0586532 is predicted to exhibit a in vivo efficacy without cardiovascular toxicity and showed the potential of non-hydroxamate LpxC inhibitors as antibacterial agents against carbapenem ...

2013年2月22日 · Inhibitors of LpxC include CHIR-090, L-161,240, BB-78485, LPC-009 (R = H), and LPC-011 (R = NH 2). FabZ (labeled in blue) is a dehydratase in fatty acid biosynthesis and shares a substrate with LpxA. Point mutations that decrease FabZ activity have been proposed to increase the flux of (R)-3-hydroxymyristoyl-ACP toward lipid A biosynthesis.

K16363 lpxC-fabZ; UDP-3-O- [3-hydroxymyristoyl] N-acetylglucosamine deacetylase / 3-hydroxyacyl- [acyl-carrier-protein] dehydratase Lipopolysaccharide biosynthesis proteins [BR: ko01005]

We have demonstrated that the target of these compounds is LpxC and that decreased susceptibility to these inhibitors can occur through mutations in the fabZ gene, whose gene product is involved in fatty-acid biosynthesis, or in the lpxC target gene. These data further validate LpxC as a target for gram-negative selective antibacterials. Go to:

Here, we perform deep mutational scanning on three essential E. coli proteins (FabZ, LpxC and MurA) involved in cell envelope synthesis using high-throughput CRISPR genome editing, and study the effect of the mutations in their original genomic context.