Molecular basis of antibiotic self-resistance in a bee larvae pathogen

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dc.contributor.authorDang, Tam
dc.contributor.authorLoll, Bernhard
dc.contributor.authorMüller, Sebastian
dc.contributor.authorSkobalj, Ranko
dc.contributor.authorEbeling, Julia
dc.contributor.authorBulatov, Timur
dc.contributor.authorGensel, Sebastian
dc.contributor.authorGöbel, Josefine
dc.contributor.authorWahl, Markus C.
dc.contributor.authorGenersch, Elke
dc.contributor.authorMainz, Andi
dc.contributor.authorSüssmuth, Roderich D.
dc.date.accessioned2022-06-27T11:43:47Z
dc.date.available2022-06-27T11:43:47Z
dc.date.issued2022-04-29
dc.description.abstractPaenibacillus larvae, the causative agent of the devastating honey-bee disease American Foulbrood, produces the cationic polyketide-peptide hybrid paenilamicin that displays antibacterial and antifungal activity. Its biosynthetic gene cluster contains a gene coding for the N-acetyltransferase PamZ. We show that PamZ acts as self-resistance factor in Paenibacillus larvae by deactivation of paenilamicin. Using tandem mass spectrometry, nuclear magnetic resonance spectroscopy and synthetic diastereomers, we identified the N-terminal amino group of the agmatinamic acid as the N-acetylation site. These findings highlight the pharmacophore region of paenilamicin, which we very recently identified as a ribosome inhibitor. Here, we further determined the crystal structure of PamZ:acetyl-CoA complex at 1.34 Å resolution. An unusual tandem-domain architecture provides a well-defined substrate-binding groove decorated with negatively-charged residues to specifically attract the cationic paenilamicin. Our results will help to understand the mode of action of paenilamicin and its role in pathogenicity of Paenibacillus larvae to fight American Foulbrood.en
dc.description.sponsorshipTU Berlin, Open-Access-Mittel – 2022en
dc.description.sponsorshipDFG, 279410221, Interdisziplinäre Studien zu nichtribosomalen Sekundärmetaboliten aus Paenibacillus larvaeen
dc.description.sponsorshipDFG, 392923329, GRK 2473: Bioaktive Peptide - Innovative Aspekte zur Synthese und Biosyntheseen
dc.identifier.eissn2041-1723
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/17164
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-15943
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftende
dc.subject.otherantimicrobial resistanceen
dc.subject.othernatural productsen
dc.subject.otherpeptidesen
dc.subject.otherstructural biologyen
dc.titleMolecular basis of antibiotic self-resistance in a bee larvae pathogenen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumber2349en
dcterms.bibliographicCitation.doi10.1038/s41467-022-29829-wen
dcterms.bibliographicCitation.journaltitleNature Communicationsen
dcterms.bibliographicCitation.originalpublishernameSpringer Natureen
dcterms.bibliographicCitation.originalpublisherplaceHeidelbergen
dcterms.bibliographicCitation.volume13en
tub.accessrights.dnbfreeen
tub.affiliationFak. 2 Mathematik und Naturwissenschaften::Inst. Chemie::FG Organische Chemiede
tub.affiliation.facultyFak. 2 Mathematik und Naturwissenschaftende
tub.affiliation.groupFG Organische Chemiede
tub.affiliation.instituteInst. Chemiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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