title: Dissecting structural and functional diversity of the lantibiotic mersacidin.
abstract: Mersacidin is a tetracyclic lantibiotic with antibacterial activity against Gram-positive pathogens. To probe the specificity of the biosynthetic pathway of mersacidin and obtain analogs with improved antibacterial activity, an efficient system for generating variants of this lantibiotic was developed. A saturation mutagenesis library of the residues of mersacidin not involved in cycle formation was constructed and used to validate this system. Mersacidin analogs were obtained in good yield in approximately 35% of the cases, producing a collection of 82 new compounds. This system was also used for the production of deletion and insertion mutants of mersacidin. The outcome of these studies suggests that this system can be extended to produce mersacidin variants with multiple changes that will allow a full investigation of the potential use of modified mersacidins as therapeutic agents.
authors.affiliation: Novacta Biosystems Ltd., Welwyn Garden City, Hertfordshire, UK.
authors.forename: Antony N
authors.initials: AN
authors.lastname: Appleyard
authors.forename: Shaila
authors.initials: S
authors.lastname: Choi
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Read
authors.forename: Ann
authors.initials: A
authors.lastname: Lightfoot
authors.forename: Steven
authors.initials: S
authors.lastname: Boakes
authors.forename: Anja
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Ian
authors.initials: I
authors.lastname: Chopra
authors.forename: Gabriele
authors.initials: G
authors.lastname: Bierbaum
authors.forename: Brian A M
authors.initials: BA
authors.lastname: Rudd
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dawson
authors.forename: Jesus
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001430:Bacteriocins / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D005810:Multigene Family; D050505:Mutant Proteins / Q000737:chemistry / Q000494:pharmacology; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D050505:Mutant Proteins; D019151:Peptide Library; D010455:Peptides; C069959:mersacidin