title: 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.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Velásquez
authors.forename: Xingang
authors.initials: X
authors.lastname: Zhang
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D015870:Gene Expression; D005798:Genes, Bacterial; D019344:Lactic Acid / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D013212:Staphylococcus epidermidis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D010455:Peptides; C500288:epilancin 15X; D019344:Lactic Acid; D000426:Alcohol Dehydrogenase