Synthetic biology of modular endolysins

Biotechnol Adv. 2018 May-Jun;36(3):624-640. doi: 10.1016/j.biotechadv.2017.12.009. Epub 2017 Dec 15.

Abstract

Endolysins and their derivatives have emerged in recent years as a novel class of antibacterials, which have now entered the clinical phases. Their rapid mode-of-action and proteinaceous nature differentiates them from any other class of antibiotics. A key feature of endolysins is their modularity and the opportunities that emerge thereof to customize properties such as specificity, activity, stability and solubility. Extensive protein engineering efforts have expanded the activity spectrum to (pan)drug-resistant Gram-negative bacteria or have improved the activity against Gram-positive pathogens. In addition, specific cell wall binding domains derived from endolysins are exploited for the development of diagnostics.

Keywords: Domain swapping; Endolysin; Engineering; Enzybiotics; Fusions; Mutagenesis; Truncation; clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Cell Wall / metabolism
  • Clinical Trials as Topic
  • Endopeptidases / chemistry*
  • Endopeptidases / genetics
  • Endopeptidases / metabolism
  • Endopeptidases / pharmacology*
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Half-Life
  • Humans
  • Mutagenesis
  • Protein Domains
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Structure-Activity Relationship
  • Synthetic Biology / methods*

Substances

  • Anti-Bacterial Agents
  • Recombinant Proteins
  • Endopeptidases
  • endolysin