Biosynthesis of the antimicrobial peptide epilancin 15X and its N-terminal lactate.

Abstract

Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides. The recently discovered lantibiotic epilancin 15X produced by Staphylococcus epidermidis 15X154 contains an unusual N-terminal lactate group. To understand its biosynthesis, the epilancin 15X biosynthetic gene cluster was identified. The N-terminal lactate is produced by dehydration of a serine residue in the first position of the core peptide by ElxB, followed by proteolytic removal of the leader peptide by ElxP and hydrolysis of the resulting new N-terminal dehydroalanine. The pyruvate group thus formed is reduced to lactate by an NADPH-dependent oxidoreductase designated ElxO. The enzymatic activity of ElxB, ElxP, and ElxO were investigated in vitro or in vivo and the importance of the N-terminal modification for peptide stability against bacterial aminopeptidases was assessed.

• Authors: Juan E Velásquez, Xingang Zhang, Wilfred A van der Donk
• Journal: Chemistry & biology (Chem Biol) Vol. 18 Issue 7 Pg. 857-67 (Jul 29 2011) ISSN: 1879-1301 [Electronic] United States
• PMID: 21802007 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Bacteriocins
• Peptides
• epilancin 15X
• Lactic Acid
• Alcohol Dehydrogenase

Topics

• Alcohol Dehydrogenase (genetics, metabolism)
• Amino Acid Sequence
• Anti-Bacterial Agents (metabolism)
• Bacterial Proteins (genetics, metabolism)
• Bacteriocins (genetics, metabolism)
• Cloning, Molecular
• Gene Expression
• Genes, Bacterial
• Lactic Acid (metabolism)
• Molecular Sequence Data
• Multigene Family
• Peptides (genetics, metabolism)
• Staphylococcus epidermidis (enzymology, genetics, metabolism)