An engineered lantibiotic synthetase that does not require a leader peptide on its substrate

Trent J. Oman, Patrick J. Knerr, Noah A. Bindman, Juan E. Velásquez, Wilfred A. Van Der Donk

Research output: Contribution to journalArticlepeer-review


Ribosomally synthesized and post-translationally modified peptides are a rapidly expanding class of natural products. They are typically biosynthesized by modification of a C-terminal segment of the precursor peptide (the core peptide). The precursor peptide also contains an N-terminal leader peptide that is required to guide the biosynthetic enzymes. For bioengineering purposes, the leader peptide is beneficial because it allows promiscuous activity of the biosynthetic enzymes with respect to modification of the core peptide sequence. However, the leader peptide also presents drawbacks as it needs to be present on the core peptide and then removed in a later step. We show that fusing the leader peptide for the lantibiotic lacticin 481 to its biosynthetic enzyme LctM allows the protein to act on core peptides without a leader peptide. We illustrate the use of this methodology for preparation of improved lacticin 481 analogues containing non-proteinogenic amino acids.

Original languageEnglish (US)
Pages (from-to)6952-6955
Number of pages4
JournalJournal of the American Chemical Society
Issue number16
StatePublished - Apr 25 2012

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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