title: Brominated Variant of the Lantibiotic NAI-107 with Enhanced Antibacterial Potency.
abstract: We identified an Actinoallomurus strain producing NAI-107, a chlorinated lantibiotic effective against multidrug-resistant Gram-positive pathogens and previously reported from the distantly related genus Microbispora. Inclusion of KBr in the production medium of either the Actinoallomurus or the Microbispora producer readily afforded brominated variants of NAI-107, which were designated as NAI-108. The other post-translational modifications naturally occurring in this lantibiotic family (i.e., hydroxylation of Pro-14 and C-terminal decarboxylation) were unaffected by the presence of a brominated tryptophan. In addition to being the first example of a bromine-containing lantibiotic, NAI-108 displayed a small but consistent improvement in antibacterial activity against all tested strains. The brominated lantibiotic maintained the same rapid bactericidal activity as NAI-107 but at reduced concentrations, consistent with its increased potency and with the role played by the hydrophobicity of the first lanthionine ring. NAI-108 thus represents an interesting addition to a promising family of potent and effective lantibiotics.
authors.affiliation: KtedoGen Srl , Viale Ortles 22/4, 20139 Milano, Italy.|University of Warwick , Coventry CV4 7AL, United Kingdom.
authors.forename: João C S
authors.initials: JC
authors.lastname: Cruz
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Iorio
authors.affiliation: KtedoGen Srl , Viale Ortles 22/4, 20139 Milano, Italy.|Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Monciardini
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Simone
authors.affiliation: University of Warwick , Coventry CV4 7AL, United Kingdom.|Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Brunati
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gaspari
authors.affiliation: KtedoGen Srl , Viale Ortles 22/4, 20139 Milano, Italy.|Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Maffioli
authors.affiliation: University of Warwick , Coventry CV4 7AL, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wellington
authors.affiliation: KtedoGen Srl , Viale Ortles 22/4, 20139 Milano, Italy.|Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sosio
authors.affiliation: KtedoGen Srl , Viale Ortles 22/4, 20139 Milano, Italy.|Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Donadio
mesh_terms: D039903:Actinobacteria / Q000737:chemistry; D000192:Actinomycetales / Q000737:chemistry; D000409:Alanine / Q000031:analogs & derivatives; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D001430:Bacteriocins / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006842:Hydrocarbons, Brominated / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D016814:Microsporidia / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides; D013440:Sulfides
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D006842:Hydrocarbons, Brominated; D010455:Peptides; D013440:Sulfides; C528150:microbisporicin; C001520:lanthionine; D000409:Alanine