Related Experiment Video
Updated: Sep 16, 2026

Production, Crystallization and Structure Determination of C. difficile PPEP-1 via Microseeding and Zinc-SAD
Published on: December 30, 2016
Pep5, a new lantibiotic: structural gene isolation and prepeptide sequence
C Kaletta1, K D Entian, R Kellner
1Institut für Mikrobiologie, Universität Frankfurt, Federal Republic of Germany.
Insights
Researchers identified the lantibiotic Pep5 gene (pepA) on plasmid pED503 using a synthetic oligonucleotide probe. This confirms Pep5 is ribosomally synthesized and reveals details about its prepeptide structure and maturation process.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Lantibiotics are ribosomally synthesized peptides with antimicrobial properties.
- Pep5 is a lantibiotic whose genetic basis and maturation pathway were previously uncharacterized.
Purpose of the Study:
- To identify and characterize the structural gene (pepA) for the lantibiotic Pep5.
- To elucidate the ribosomal synthesis and maturation process of Pep5.
Main Methods:
- Oligonucleotide probe design based on the Pep5 propeptide sequence.
- Hybridization screening to locate the pepA gene on plasmid pED503.
- Nucleotide sequencing of the pepA gene.
Main Results:
- The structural gene pepA was identified on the 18.6 kbp plasmid pED503.
- Nucleotide sequencing revealed pepA codes for a 60-residue prepeptide, confirming ribosomal synthesis.
- The prepeptide N-terminus exhibits alpha-helix probability, with a cleavage site preceding the 34-residue propeptide.
Conclusions:
- Pep5 is confirmed to be ribosomally synthesized.
- The maturation of Pep5 likely involves enzymatic modification of amino acids and proteolytic cleavage.
- A model for Pep5 maturation includes dehydration, sulfide bridge formation, translocation, and cleavage.
Abstract:
A wobbled 14-mer oligonucleotide was derived from the amino acid sequence of the 34-residue propeptide of the lantibiotic Pep5 (Kellner et al. 1989). Using this hybridization probe, the structural gene of Pep5, pepA, was located on the 18.6 kbp plasmid pED503. The nucleotide sequence of pepA codes for a prepeptide with 60 residues and proves that Pep5 is ribosomally synthesized. The N-terminus of the prepeptide has a high alpha-helix probability and a characteristic proteolytic cleavage site precedes the C-terminal 34-residue propeptide. Our present theory is that maturation of Pep5 involves (a) enzymic conversion of Thr, Ser and Cys into dehydrated amino acids and sulfide bridges, (b) membrane translocation and cleavage of the modified prepeptide.
Related Concept Videos
Peptidoglycan Synthesis
Development of Antibiotic Resistance
Production of Antibiotics
Production of Pharmaceuticals
Inhibitors of Gram-positive Cell Wall Synthesis

