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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Methodologies and Strategies for the Bioengineering of Lantibiotics

Author(s): Jun-ichi Nagao, Mami Nishie and Kenji Sonomoto

Volume 12, Issue 8, 2011

Page: [1221 - 1230] Pages: 10

DOI: 10.2174/138920111796117355

Price: $65

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Abstract

Lantibiotics are ribosomally synthesized, post-translationally modified, peptide antibiotics containing unusual amino acids such as dehydrated amino acids and lanthionine. These unusual amino acids impose conformational constraints on the peptide and contribute to the biological activity and high physicochemical stability of lantibiotics. Recent researches on the modification enzymes responsible for dehydration and cyclization have considerably increased our understanding of their molecular characteristics and relaxed specificity. These insights enabled us to exploit these modification enzymes for developing new lantibiotic variants with improved therapeutic potential. Several methodologies have been explored to engineer novel lantibiotics. Here, we outline the current knowledge of modification enzymes. We also describe the methodologies and strategies used to engineer lantibiotics and provide some examples of successful generation of lantibiotics with enhanced activity.

Keywords: Cyclization, dehydration, lantibiotics, modification enzyme, peptide engineering, unusual amino acid, conformational constraint, physicochemical stability, relaxed specificity, IN VIVO ENGINEERING, ATP binding cassette, Bioengineering of Lantibiotics


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