Generation of thiocillin ring size variants by prepeptide gene replacement and in vivo processing by Bacillus cereus

J Am Chem Soc. 2012 Jun 27;134(25):10313-6. doi: 10.1021/ja302820x. Epub 2012 Jun 15.

Abstract

The thiocillins from Bacillus cereus ATCC 14579 are natural products from the broader class of thiazolyl peptides. Their biosynthesis proceeds via extensive post-translational modification of a ribosomally encoded precursor peptide. This post-translational tailoring involves a key step formal cycloaddition between two distal serine residues. In the wild-type structure, this cycloaddition forms a major macrocycle circumscribed by 26-atoms (shortest path). Results presented herein demonstrate the promiscuity of this last step by means of a set of "competition" experiments. Cyclization proceeds in many cases to provide altered ring sizes, giving access to several variant rings sizes that have not previously been observed in nature.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Bacillus cereus* / genetics
  • Cyclization
  • Genetic Variation
  • Molecular Structure
  • Peptides / chemistry
  • Peptides / genetics*
  • Protein Processing, Post-Translational

Substances

  • Anti-Bacterial Agents
  • Peptides
  • thiocillin