In vitro mutasynthesis of lantibiotic analogues containing nonproteinogenic amino acids

Matthew R. Levengood, Patrick J. Knerr, Trent J. Oman, Wilfred A. Van Der Donk

Research output: Contribution to journalArticle


(Figure Presented) Lantibiotics are ribosomally synthesized and post-translationally modified peptide antibiotics containing the characteristic thioether cross-links lanthionine and methyllanthionine. To date, no analogues of lantibiotics that contain nonproteinogenic amino acids have been reported. In this study, in vitro-reconstituted lacticin 481 synthetase was used in conjunction with synthetic peptide substrates containing nonproteinogenic amino acids to generate 11 analogues of lacticin 481. These analogues contained sarcosine and aminocyclopropanoic acid in place of Gly5, D-valine at position 6, 4-cyanoaminobutyric acid in place of Glu13, β3-homoarginine at the position of Asn15, N-butylglycine and β-Ala at Met16, naphthylalanine (Nal) at Trp19, 4-pyridynylalanine (Pal) at Phe21, and homophenylalanine (hPhe) at Phe23. Of these analogues, the Trp19Nal and Phe23hPhe mutants provided zones of inhibition larger than the parent compound in agar diffusion assays against the indicator strains Lactococcus lactis HP and Bacillus subtilis 6633. These two compounds also demonstrated improved MIC values against liquid cultures of L. lactis HP.

Original languageEnglish (US)
Pages (from-to)12024-12025
Number of pages2
JournalJournal of the American Chemical Society
Issue number34
StatePublished - Sep 2 2009

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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