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 Lubelski, J.
Right arrow Articles by Kuipers, O. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lubelski, J.
Right arrow Articles by Kuipers, O. P.
Agricola
Right arrow Articles by Lubelski, J.
Right arrow Articles by Kuipers, O. P.

 Previous Article  |  Next Article 

Applied and Environmental Microbiology, August 2008, p. 4680-4685, Vol. 74, No. 15
0099-2240/08/$08.00+0     doi:10.1128/AEM.00112-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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{triangledown} ,{dagger}

Jacek Lubelski,1 Wout Overkamp,1 Leon D. Kluskens,2 Gert N. Moll,2 and Oscar P. Kuipers1*

Molecular Genetics Department, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands,1 BiOMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, The Netherlands2

Received 14 January 2008/ Accepted 7 April 2008

Since the recent discovery that the nisin modification and transport machinery can be used to produce and modify peptides unrelated to nisin, specific questions arose concerning the specificity of the modification enzymes involved and the limits of their promiscuity with respect to the dehydration and cyclization processes. The nisin leader peptide has been postulated to fulfill a recognition and binding function required for these modifications. Here, we investigated whether the relative positions of the modifiable residues in the nisin prepeptide, with respect to the leader peptide, could influence the efficiency of their modification. We conducted a systematic study on the insertion of one to four alanines in front of either ring A or ring D to change the "reading frame" of modifiable residues, resulting in altered distance and topology of the modifiable residues relative to the leader. The insertion of N-terminal and hinge-located Ala residues had only a modest influence on the modification efficiency, demonstrating that the "phasing" of these residues relative to the leader peptide is not a critical factor in determining modification. However, in all cases, but especially with the N-terminal insertions, the antimicrobial activities of the fully modified nisin species were decreased.

* Corresponding author. Mailing address: Molecular Genetics Department, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands. Phone: 31 50 3632093. Fax: 31 50 3632348. E-mail: o.p.kuipers{at}rug.nl

{triangledown} Published ahead of print on 6 June 2008.

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

Applied and Environmental Microbiology, August 2008, p. 4680-4685, Vol. 74, No. 15
0099-2240/08/$08.00+0     doi:10.1128/AEM.00112-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lubelski, J., Khusainov, R., Kuipers, O. P. (2009). Directionality and Coordination of Dehydration and Ring Formation during Biosynthesis of the Lantibiotic Nisin. J. Biol. Chem. 284: 25962-25972 [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»