Lichenicidin rational site-directed mutagenesis library: a tool to generate bioengineered lantibiotics

Joana Barbosa, Tânia Caetano, Eva Mösker, Roderich Süssmuth, Sónia Mendo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that arise as an alternative to the traditional antibiotics. Lichenicidin is active against clinically relevant bacteria and it was the first lantibiotic to be fully produced in vivo in the Gram-negative host Escherichia coli. Here, we present the results of a library of lichenicidin mutants, in which the mutations were generated based on the extensive bibliographical search available for other lantibiotics. The antibacterial activity of two-peptide lantibiotics, as is lichenicidin, requires the synergistic activity of two peptides. We established a method that allows screening for bioactivity which does not require the purification of the complementary peptide. It is an inexpensive, fast and user-friendly method that can be scaled up to screen large libraries of bioengineered two-peptide lantibiotics. The applied system is reliable and robust because, in general, the results obtained corroborate structure–activity relationship studies carried out for other lantibiotics.

Original languageEnglish
Pages (from-to)3053-3062
Number of pages10
JournalBiotechnology and Bioengineering
Volume116
Issue number11
DOIs
Publication statusPublished - 1 Nov 2019
Externally publishedYes

Keywords

  • Heterologous expression
  • Lanthipeptides
  • Ssite-directed mutagenesis

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