TY - JOUR
T1 - Biosynthesis of the antimicrobial peptide epilancin 15X and its N-terminal lactate
AU - Velásquez, Juan E.
AU - Zhang, Xingang
AU - Van Der Donk, Wilfred A.
N1 - Funding Information:
We thank M. Ekkelenkamp and Prof. J. Verhoef (Utrecht University Hospital) for a sample of S. epidermidis 15X154, and William Metcalf and Mr. Jun Kai Zhang for helpful advice on molecular genetics and for the strains and plasmids used for generating the genomic library. We also thank Ms. Laura Guest at the Core DNA Sequencing Facility, Ms. Neha Garg for help in the screening of the genomic library, and Ms. Isabel Neacato for help in cloning. This work was supported by a grant from the National Institutes of Health (GM58822 to W.A.v.d.D.). J.E.V. was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award T32 GM070421.
PY - 2011/7/29
Y1 - 2011/7/29
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2011.05.007
DO - 10.1016/j.chembiol.2011.05.007
M3 - Article
C2 - 21802007
AN - SCOPUS:79960963680
SN - 1074-5521
VL - 18
SP - 857
EP - 867
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 7
ER -