PMID:17660303
| Citation |
Rink, R, Wierenga, J, Kuipers, A, Kluskens, LD, Driessen, AJ, Kuipers, OP and Moll, GN (2007) Dissection and modulation of the four distinct activities of nisin by mutagenesis of rings A and B and by C-terminal truncation. Appl. Environ. Microbiol. 73:5809-16 |
|---|---|
| Abstract |
Nisin A is a pentacyclic antibiotic peptide produced by various Lactococcus lactis strains. Nisin displays four different activities: (i) it autoinduces its own synthesis; (ii) it inhibits the growth of target bacteria by membrane pore formation; (iii) it inhibits bacterial growth by interfering with cell wall synthesis; and, in addition, (iv) it inhibits the outgrowth of spores. Here we investigate the structural requirements and relevance of the N-terminal thioether rings of nisin by randomization of the ring A and B positions. The data demonstrate that: (i) mutation of ring A results in variants with enhanced activity and a modulated spectrum of target cells; (ii) for the cell growth-inhibiting activity of nisin, ring A is rather promiscuous with respect to its amino acid composition, whereas the bulky amino acid residues in ring B abolish antimicrobial activity; (iii) C-terminally truncated nisin A mutants lacking rings D and E retain significant antimicrobial activity but are unable to permeabilize the target membrane; (iv) the dehydroalanine in ring A is not essential for the inhibition of the outgrowth of Bacillus cells; (v) some ring A mutants have significant antimicrobial activities but have decreased autoinducing activities; (vi) the opening of ring B eliminates antimicrobial activity while retaining autoinducing activity; and (vii) some ring A mutants escape the nisin immune system(s) and are toxic to the nisin-producing strain NZ9700. These data demonstrate that the various activities of nisin can be engineered independently and provide a basis for the design and synthesis of tailor-made analogs with desired activities. |
| Links |
PubMed PMC2074915 Online version:10.1128/AEM.01104-07 |
| Keywords |
Anti-Bacterial Agents/biosynthesis; Anti-Bacterial Agents/chemistry; Bacteria/drug effects; Bacteria/growth & development; Bacterial Proteins; Mutagenesis; Mutagenesis, Site-Directed; Nisin/biosynthesis; Nisin/chemistry; Nisin/genetics; Nisin/pharmacology; Protein Conformation; Protein Engineering/methods; Recombinant Proteins/chemistry; Recombinant Proteins/pharmacology; Structure-Activity Relationship |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.