AEM Accepts, published online ahead of print on 19 January 2007

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Appl. Environ. Microbiol. doi:10.1128/AEM.02350-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Production of dehydroamino acid-containing peptides by Lactococcus lactis

Rick Rink, Jenny Wierenga, Anneke Kuipers, Leon D. Kluskens, Arnold J.M. Driessen, Oscar P. Kuipers, and Gert N. Moll^*

BiOMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, The Netherlands and; Department of Microbiology, Kerklaan 30, 9751 NN Haren and; Department of Molecular Genetics, Kerklaan 30, 9751 NN Haren, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, The Netherlands

^* To whom correspondence should be addressed. Email: Moll{at}biomade.nl.

Nisin is a pentacyclic peptide antibiotic produced by some Lactococcus lactis strains. Nisin contains dehydroresidues and thioether rings that are posttranslationally introduced by a membrane-associated enzyme complex, composed of a serine and threonine dehydratase NisB, and the cyclase NisC. In addition, the transporter NisT is necessary for export of the modified peptide. We studied the potential of L. lactis expressing NisB and NisT to produce peptides whose serines and threonines are dehydrated. L. lactis containing the nisBT genes and a plasmid coding for a specific leader peptide fusion construct efficiently produced peptides with a series of non-naturally occurring multiple flanking dehydrobutyrines. We demonstrated NisB-mediated dehydration of serines and threonines in a C-terminal nisin(1-14) extension of nisin, which implies that also residues more distant from the leader peptide than those occurring in prenisin or any other lantibiotic can be modified. Furthermore, the feasibility and efficiency of generating a library of peptides containing dehydroresidues was demonstrated. In view of the particular shape and reactivity of dehydroamino acids such a library provides a novel source for screening for peptides with desired biological and physico-chemical properties.

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