Publication

Analysis of modular bioengineered antimicrobial lanthipeptides at nanoliter scale

Schmitt, S., Montalbán-López, M., Peterhoff, D., Deng, J., Wagner, R., Held, M., Kuipers, O. P. & Panke, S., May-2019, In : Nature Chemical Biology. 15, 5, p. 437-443 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Steven Schmitt
  • Manuel Montalbán-López
  • David Peterhoff
  • Jingjing Deng
  • Ralf Wagner
  • Martin Held
  • Oscar P Kuipers
  • Sven Panke

The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino acid lanthionine. New-to-nature variants featuring distinct properties were obtained by combinatorial shuffling of peptide modules derived from 12 natural antimicrobial lanthipeptides and processing by a promiscuous post-translational modification machinery. For experimental characterization, we developed the nanoFleming, a miniaturized and parallelized high-throughput inhibition assay. On the basis of a hit set of >100 molecules, we identified variants with improved activity against pathogenic bacteria and shifted activity profiles, and extrapolated design guidelines that will simplify the identification of peptide-based anti-infectives in the future.

Original languageEnglish
Pages (from-to)437-443
Number of pages8
JournalNature Chemical Biology
Volume15
Issue number5
Early online date1-Apr-2019
Publication statusPublished - May-2019

    Keywords

  • NATURAL-PRODUCTS, PEPTIDE, NISIN, BIOSYNTHESIS, LANTIBIOTICS, PROTEIN, LEADER, PROMISCUITY, MACHINERY, PLATFORM
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