title: Discovery and Characterization of Bicereucin, an Unusual d-Amino Acid-Containing Mixed Two-Component Lantibiotic.
abstract: Lantibiotics are a group of ribosomally synthesized and post-translationally modified peptides (RiPPs) exhibiting antimicrobial activity. They are characterized by the presence of the thioether-containing bisamino acids lanthionine and methyllanthionine. Here, we report a two-component lantibiotic from Bacillus cereus SJ1 with unusual structural features that we named bicereucin. Unlike all previous two-component lantibiotics, only one of the two peptides of bicereucin contains a lanthionine. The second peptide lacks any cysteines but contains several d-amino acids. These are installed by the dehydrogenase BsjJB, the activity of which was successfully reconstituted in vitro. The proteolytic removal of the leader peptide was also performed in vitro. Bicereucin displayed synergistic antimicrobial activities against Gram-positive strains including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci as well as hemolytic activity. To illustrate the utility of the enzymes, an analog of the d-amino acid containing opioid dermorphin was successfully produced in E. coli by employing the dehydratase BsjM and the dehydrogenase NpnJA.
authors.affiliation: Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign , 600 S. Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Liujie
authors.initials: L
authors.lastname: Huo
authors.affiliation: Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign , 600 S. Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001409:Bacillus cereus / Q000235:genetics / Q000378:metabolism*; D001430:Bacteriocins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010088:Oxidoreductases / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D021382:Protein Sorting Signals; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D013440:Sulfides; D010088:Oxidoreductases; C001520:lanthionine; D003545:Cysteine; D000409:Alanine