De-novo designed β-lysine derivatives can both augment and diminish the proliferation rates of E. coli through the action of Elongation Factor P

Bioorg Med Chem Lett. 2022 Mar 1:59:128545. doi: 10.1016/j.bmcl.2022.128545. Epub 2022 Jan 12.

Abstract

An investigation into the effect of modified β-lysines on the growth rates of eubacterial cells is reported. It is shown that the effects observed are due to the post translational modification of Elongation Factor P (EFP) with these compounds catalysed by PoxA. PoxA was found to be remarkably promiscuous, which allowed the activity of a wide range of exogenous β-lysines to be examined. Two chain-elongated β-lysine derivatives which differ in aminoalkyl chain length by only 2 carbon units exhibited opposing biological activities - one promoting growth and the other retarding it. Both compounds were shown to operate through modification of EFP.

Keywords: Antibacterial agents; Elongation factor P; Peptide synthesis; Ribosome stalling; β-Lysine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Deoxyribonucleases / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Escherichia coli / cytology
  • Escherichia coli / drug effects*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / metabolism*
  • Lysine / analogs & derivatives*
  • Lysine / chemical synthesis
  • Lysine / chemistry
  • Lysine / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Protein Processing, Post-Translational
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • beta-lysine
  • Deoxyribonucleases
  • yjeA protein, E coli
  • Lysine