Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin

Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2549-53. doi: 10.1073/pnas.0900008106. Epub 2009 Feb 5.

Abstract

The thiazolylpeptides are a family of >50 bactericidal antibiotics that block the initial steps of bacterial protein synthesis. Here, we report a biosynthetic gene cluster for thiocillin and establish that it, and by extension the whole class, is ribosomally synthesized. Remarkably, the C-terminal 14 residues of a 52-residue peptide precursor undergo 13 posttranslational modifications to give rise to thiocillin, making this antibiotic the most heavily posttranslationally-modified peptide known to date.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacillus cereus / genetics
  • Chromatography, High Pressure Liquid
  • Computational Biology
  • Mass Spectrometry
  • Molecular Sequence Data
  • Multigene Family
  • Mutagenesis, Insertional
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Peptides / chemical synthesis*
  • Peptides / genetics
  • Peptides / pharmacology
  • Protein Processing, Post-Translational*

Substances

  • Oligopeptides
  • Peptides
  • thiocillin