Obtaining an Ent35-MccV derivative with mutated hinge region that exhibits increased activity against Listeria monocytogenes and Escherichia coli

Appl Microbiol Biotechnol. 2019 Dec;103(23-24):9607-9618. doi: 10.1007/s00253-019-10187-5. Epub 2019 Nov 12.

Abstract

The present paper describes the generation of derivatives from the hybrid peptide called Ent35-MccV, active against Gram-positive and Gram-negative bacteria. This peptide has a triple glycine hinge region between enterocin CRL35 and microcin V. In order to obtain variants of Ent35-MccV with greater biotechnological potential, a saturation mutagenesis was carried out in the hinge region. As a result, we obtained a bank of E. coli strains expressing different mutated hybrid bacteriocins in the central position of the hinge region. From all these variants, we found that the one bearing a tyrosine in the central region of the hinge (Ent35-GYG-MccV) is 2-fold more active against E. coli and 4-fold more active against Listeria than the original peptide Ent35-MccV. This derivative was purified and characterized. The development and evaluation of alternative hinges for Ent35-MccV represents a step forward in the bioengineering of antimicrobial peptides. This approach fosters the rational design of peptides with enhanced antimicrobial activity.

Keywords: ANTIMICROBIAL ACTIVITY; ENTEROCIN CRL35; HINGE REGION; HYBRID PEPTIDE; MICROCIN V; MUTAGENESIS.

MeSH terms

  • Amino Acid Sequence
  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / metabolism
  • Anti-Infective Agents / pharmacology*
  • Bacteriocins / genetics
  • Bacteriocins / metabolism
  • Bacteriocins / pharmacology*
  • Escherichia coli / drug effects*
  • Listeria monocytogenes / drug effects*
  • Microbial Viability / drug effects
  • Mutagenesis, Site-Directed
  • Mutation
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology

Substances

  • Anti-Infective Agents
  • Bacteriocins
  • Recombinant Fusion Proteins
  • enterocin CRL35
  • microcin