This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rink, R.
Right arrow Articles by Moll, G. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rink, R.
Right arrow Articles by Moll, G. N.
Agricola
Right arrow Articles by Rink, R.
Right arrow Articles by Moll, G. N.

 Previous Article  |  Next Article 

Applied and Environmental Microbiology, September 2007, p. 5809-5816, Vol. 73, No. 18
0099-2240/07/$08.00+0     doi:10.1128/AEM.01104-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Dissection and Modulation of the Four Distinct Activities of Nisin by Mutagenesis of Rings A and B and by C-Terminal Truncation{triangledown} ,{dagger}

Rick Rink,1 Jenny Wierenga,1 Anneke Kuipers,1 Leon D. Kluskens,1 Arnold J. M. Driessen,2 Oscar P. Kuipers,3 and Gert N. Moll1*

BiOMaDe Technology Foundation, Groningen, The Netherlands,1 Department of Microbiology,2 Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands3

Received 17 May 2007/ Accepted 21 July 2007

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.

* Corresponding author. Mailing address: BiOMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, The Netherlands. Phone: 31 50 363 80 70. Fax: 31 50 363 44 29. E-mail: Moll{at}biomade.nl

{triangledown} Published ahead of print on 27 July 2007.

{dagger} Supplemental material for this article may be found at http://aem.asm.org/.

Applied and Environmental Microbiology, September 2007, p. 5809-5816, Vol. 73, No. 18
0099-2240/07/$08.00+0     doi:10.1128/AEM.01104-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gut, I. M., Prouty, A. M., Ballard, J. D., van der Donk, W. A., Blanke, S. R. (2008). Inhibition of Bacillus anthracis Spore Outgrowth by Nisin. Antimicrob. Agents Chemother. 52: 4281-4288 [Abstract] [Full Text]  
  • Kuipers, A., Meijer-Wierenga, J., Rink, R., Kluskens, L. D., Moll, G. N. (2008). Mechanistic Dissection of the Enzyme Complexes Involved in Biosynthesis of Lacticin 3147 and Nisin. Appl. Environ. Microbiol. 74: 6591-6597 [Abstract] [Full Text]  
  • van den Berg van Saparoea, H. B., Bakkes, P. J., Moll, G. N., Driessen, A. J. M. (2008). Distinct Contributions of the Nisin Biosynthesis Enzymes NisB and NisC and Transporter NisT to Prenisin Production by Lactococcus lactis. Appl. Environ. Microbiol. 74: 5541-5548 [Abstract] [Full Text]  
  • Lubelski, J., Overkamp, W., Kluskens, L. D., Moll, G. N., Kuipers, O. P. (2008). Influence of Shifting Positions of Ser, Thr, and Cys Residues in Prenisin on the Efficiency of Modification Reactions and on the Antimicrobial Activities of the Modified Prepeptides. Appl. Environ. Microbiol. 74: 4680-4685 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»