title: Self resistance to the atypical cationic antimicrobial peptide edeine of Brevibacillus brevis Vm4 by the N-acetyltransferase EdeQ.
abstract: Edeines are atypical cationic peptides produced by Brevibacillus brevis Vm4 with broad-spectrum antimicrobial activity. These linear nonribosomal peptides bind to the 30S ribosomal subunit and block t-RNA binding to the P-site. To identify the mechanism of high-level self-resistance in the producing organism, the B. brevis Vm4 genome was sequenced and the edeine biosynthetic cluster discovered. A potential edeine-modifying enzyme, EdeQ, showed similarity to spermidine N-acetyltransferases. EdeQ was purified and shown to convert edeine to N-acetyledeine, which is inactive against cells in vivo and against cell-free extracts. Unexpectedly, tandem mass spectroscopy and nuclear magnetic resonance demonstrate that N-acylation occurs on the free amine of the internal diaminopropionic acid rather than the N-terminal spermidine polyamine. Acetylation of edeine by EdeQ abolishes its ability to inhibit translation, thus conferring resistance to the antibiotic in the producing organism.
authors.affiliation: M. G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, 1280 Main Street W, Hamilton, ON L8N 4K1, Canada.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Westman
authors.forename: Marie
authors.initials: M
authors.lastname: Yan
authors.forename: Nicholas
authors.initials: N
authors.lastname: Waglechner
authors.forename: Kalinka
authors.initials: K
authors.lastname: Koteva
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Wright
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D058675:Brevibacillus / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D004486:Edeine / Q000737:chemistry / Q000378:metabolism*; D005798:Genes, Bacterial; D008958:Models, Molecular; D005810:Multigene Family; D019384:Nucleic Acid Synthesis Inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D019384:Nucleic Acid Synthesis Inhibitors; D004486:Edeine; D000123:Acetyltransferases