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dc.contributor.authorHug, Joachim J.
dc.contributor.authorDastbaz, Jan
dc.contributor.authorAdam, Sebastian
dc.contributor.authorRevermann, Ole
dc.contributor.authorKoehnke, Jesko
dc.contributor.authorKrug, Daniel
dc.contributor.authorMüller, Rolf
dc.date.accessioned2020-09-21T14:13:12Z
dc.date.available2020-09-21T14:13:12Z
dc.date.issued2020-07-08
dc.identifier.citationACS Chem Biol. 2020;15(8):2221-2231. doi:10.1021/acschembio.0c00430.en_US
dc.identifier.issn1554-8929
dc.identifier.pmid32639716
dc.identifier.doi10.1021/acschembio.0c00430
dc.identifier.urihttp://hdl.handle.net/10033/622447
dc.description.abstractCittilins are secondary metabolites from myxobacteria comprised of three l-tyrosines and one l-isoleucine forming a bicyclic tetrapeptide scaffold with biaryl and aryl-oxygen-aryl ether bonds. Here we reveal that cittilins belong to the ribosomally synthesized and post-translationally modified peptide (RiPP) family of natural products, for which only the crocagins have been reported from myxobacteria. A 27 amino acid precursor peptide harbors a C-terminal four amino acid core peptide, which is enzymatically modified and finally exported to yield cittilins. The small biosynthetic gene cluster responsible for cittilin biosynthesis also encodes a cytochrome P450 enzyme and a methyltransferase, whereas a gene encoding a prolyl endopeptidase for the cleavage of the precursor peptide is located outside of the cittilin biosynthetic gene cluster. We confirm the roles of the biosynthetic genes responsible for the formation of cittilins using targeted gene inactivation and heterologous expression in Streptomyces ssp. We also report first steps toward the biochemical characterization of the proposed biosynthetic pathway in vitro. An investigation of the cellular uptake properties of cittilin A connected it to a potential biological function as an inhibitor of the prokaryotic carbon storage regulator A (CsrA).en_US
dc.description.sponsorshipBundesministerium für Bildung und Forschungen_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectMolecular Medicineen_US
dc.subjectBiochemistryen_US
dc.subjectGeneral Medicineen_US
dc.titleBiosynthesis of Cittilins, Unusual Ribosomally Synthesized and Post-translationally Modified Peptides from Myxococcus xanthusen_US
dc.typeArticleen_US
dc.identifier.eissn1554-8937
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalACS chemical biologyen_US
dc.identifier.pii10.1021/acschembio.0c00430
dc.source.volume15
dc.source.issue8
dc.source.beginpage2221
dc.source.endpage2231
refterms.dateFOA2020-09-21T14:13:12Z
dc.source.journaltitleACS Chemical Biology


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