Designing and producing modified, new-to-nature peptides with antimicrobial activity by use of a combination of various lantibiotic modification enzymes

ACS Synth Biol. 2013 Jul 19;2(7):397-404. doi: 10.1021/sb3001084. Epub 2013 Feb 12.

Abstract

Lanthipeptides are peptides that contain several post-translationally modified amino acid residues and commonly show considerable antimicrobial activity. After translation, the amino acid residues of these peptides are modified by a distinct set of modification enzymes. This process results in peptides containing one or more lanthionine rings and dehydrated Ser and Thr residues. Previously, an in vivo lanthipeptide production system based on the modification machinery of the model lantibiotic nisin was reported. Here, we present the addition of the modification enzymes LtnJ and GdmD to this production system. With these enzymes we can now produce lanthipeptides that contain d-alanines or a C-terminal aminovinyl-cysteine. We show experimentally that the decarboxylase GdmD is responsible for the C-terminal decarboxylation. Our results demonstrate that different lanthipeptide modification enzymes can work together in an in vivo production system. This yields a plug-and-play system that can be used to select different sets of modification enzymes to work on diverse, specifically designed substrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / metabolism
  • Bacterial Proteins / genetics*
  • Bacteriocins / genetics*
  • Bacteriocins / isolation & purification
  • Bacteriocins / metabolism*
  • Cloning, Molecular / methods
  • Drug Design*
  • Lactococcus lactis / physiology*
  • Multienzyme Complexes / genetics*
  • Protein Engineering / methods*
  • Recombinant Proteins / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Bacteriocins
  • Multienzyme Complexes
  • Recombinant Proteins