Lacticin 481 synthetase as a general serine/threonine kinase

Ok You Young, Matthew R. Levengood, L. A.Furgerson Ihnken, Aaron K. Knowlton, Wilfred A. Van Der Donk

Research output: Contribution to journalArticlepeer-review


Methods that introduce posttranslational modifications in a general, mild, and non-sequence-specific manner using biologically produced peptides have great utility for investigation of the functions of these modifications. In this study, the substrate promiscuity of a lantibiotic synthetase was exploited for the preparation of phosphopeptides, glycopeptides, and peptides containing analogs of methylated or acetylated lysine residues. Peptides attached to the C-terminus of the leader peptide of the lacticin 481 precursor peptide were phosphorylated on serine residues in a wide variety of sequence contexts by the R399M and T405A mutants of lacticin 481 synthetase (LctM). Serine residues located as many as 30 amino acids C-terminal to the leader peptide were phosphorylated. Wild-type LctM was shown to dehydrate these peptides to generate dehydroalanine-containing products that can be conveniently modified with external nucleophiles including thiosaccharides, 2-(dimethylamino)ethanethiol, and N-acetyl cysteamine, resulting in mimics of O-linked glycopeptides and acetylated and methylated lysines.

Original languageEnglish (US)
Pages (from-to)379-385
Number of pages7
JournalACS chemical biology
Issue number5
StatePublished - May 15 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine


Dive into the research topics of 'Lacticin 481 synthetase as a general serine/threonine kinase'. Together they form a unique fingerprint.

Cite this