Journal Article


R Paul Ross
Paul D. Cotter
Colin Hill
Paula M. O’Connor
Des Field
Paula M. O'Connor
Brian Healy



peptide synthesis nisin cell wall pharmacology variant mode immunity peptides precursor lipid ii lantibiotics microbial sensitivity tests amino acid substitution anti bacterial agents staphylococcus aureus bacteriocins amino acid lactococcus lactis antibiotics chemistry genetics amino acid sequence mutagenesis lantibiotic nisin nisin a biosynthesis

Intensive Mutagenesis of the Nisin Hinge Leads to the Rational Design of Enhanced Derivatives (2013)

Abstract Nisin A is the most extensively studied lantibiotic and has been used as a preservative by the food industry since 1953. This 34 amino acid peptide contains three dehydrated amino acids and five thioether rings. These rings, resulting from one lanthionine and four methyllanthionine bridges, confer the peptide with its unique structure. Nisin A has two mechanisms of action, with the N-terminal domain of the peptide inhibiting cell wall synthesis through lipid II binding and the C-terminal domain responsible for pore-formation. The focus of this study is the three amino acid ‘hinge’ region (N 20, M 21 and K 22) which separates these two domains and allows for conformational flexibility. As all lantibiotics are gene encoded, novel variants can be generated through manipulation of the corresponding gene. A number of derivatives in which the hinge region was altered have previously been shown to possess enhanced antimicrobial activity. Here we take this approach further by employing simultaneous, indiscriminate site-saturation mutagenesis of all three hinge residues to create a novel bank of nisin derivative producers. Screening of this bank revealed that producers of peptides with hinge regions consisting of AAK, NAI and SLS displayed enhanced bioactivity against a variety of targets. These and other results suggested a preference for small, chiral amino acids within the hinge region, leading to the design and creation of producers of peptides with hinges consisting of AAA and SAA. These producers, and the corresponding peptides, exhibited enhanced bioactivity against Lactococcus lactis HP, Streptococcus agalactiae ATCC 13813, Mycobacterium smegmatis MC2155 and Staphylococcus aureus RF122 and thus represent the first example of nisin derivatives that possess enhanced activity as a consequence of rational design.
Collections Ireland -> University College Cork -> APC Microbiome Institute
Ireland -> Teagasc -> Food Biosciences
Ireland -> University College Cork -> College of Science, Engineering and Food Science
Ireland -> University College Cork -> APC Microbiome Institute- Journal Articles
Ireland -> University College Cork -> Microbiology
Ireland -> Teagasc -> Food Programme
Ireland -> University College Cork -> Research Institutes and Centres
Ireland -> University College Cork -> Microbiology - Journal Articles

Full list of authors on original publication

R Paul Ross, Paul D. Cotter, Colin Hill, Paula M. O’Connor, Des Field, Paula M. O'Connor, Brian Healy

Experts in our system

R Paul Ross
Total Publications: 441
Paul D. Cotter
Total Publications: 253
Colin Hill
University College Cork
Total Publications: 351
Des Field
Total Publications: 30
Paula M. O'Connor
Total Publications: 85