title: The Albicidin Resistance Factor AlbD Is a Serine Endopeptidase That Hydrolyzes Unusual Oligoaromatic-Type Peptides.
abstract: The para-aminobenzoic acid-containing peptide albicidin is a pathogenicity factor synthesized by Xanthomonas albilineans in infections of sugar cane. Albicidin is a nanomolar inhibitor of the bacterial DNA gyrase with a strong activity against various Gram-negative bacteria. The bacterium Pantoea dispersa expresses the hydrolase AlbD, conferring natural resistance against albicidin. We show that AlbD is a novel type of endopeptidase that catalyzes the cleavage of albicidin at a peptide backbone amide bond, thus abolishing its antimicrobial activity. Additionally, we determined the minimal cleavage motif of AlbD with substrates derived by chemical synthesis. Our results clearly identify AlbD as a unique endopeptidase that is the first member of a new subfamily of peptidases. Our findings provide the molecular basis for a natural detoxification mechanism, potentially rendering a new tool in biological chemistry approaches.
authors.affiliation: †Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Vieweg
authors.affiliation: †Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Kretz
authors.affiliation: †Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pesic
authors.affiliation: †Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kerwat
authors.affiliation: †Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Grätz
authors.affiliation: ‡CIRAD, UMR BGPI, TA A-54/K, Campus International de Baillarguet, F-34398 Montpellier cedex 5, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Royer
authors.affiliation: ‡CIRAD, UMR BGPI, TA A-54/K, Campus International de Baillarguet, F-34398 Montpellier cedex 5, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cociancich
authors.affiliation: †Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Andi
authors.initials: A
authors.lastname: Mainz
authors.affiliation: †Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D006868:Hydrolysis; D009930:Organic Chemicals / Q000378:metabolism / Q000494:pharmacology; D020636:Pantoea / Q000187:drug effects / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D014974:Xanthomonas / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D009930:Organic Chemicals; C046156:albicidin; D012697:Serine Endopeptidases