title: Methodologies and strategies for the bioengineering of lantibiotics.
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.
authors.affiliation: Section of Infection Biology, Department of Functional Bioscience, Fukuoka Dental College, 2-15-1 Tamura, Sawaraku, Fukuoka 814-0193, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nagao
authors.forename: Mami
authors.initials: M
authors.lastname: Nishie
authors.forename: Kenji
authors.initials: K
authors.lastname: Sonomot
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001430:Bacteriocins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D015202:Protein Engineering / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins