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dc.contributor.authorAdam, Sebastian
dc.contributor.authorZheng, Dazhong
dc.contributor.authorKlein, Andreas
dc.contributor.authorVolz, Carsten
dc.contributor.authorMullen, William
dc.contributor.authorShirran, Sally L.
dc.contributor.authorSmith, Brian O.
dc.contributor.authorKalinina, Olga V.
dc.contributor.authorMüller, Rolf
dc.contributor.authorKoehnke, Jesko
dc.date.accessioned2023-04-05T10:30:08Z
dc.date.available2023-04-05T10:30:08Z
dc.date.issued2023-04-01
dc.identifier.citationAdam , S , Zheng , D , Klein , A , Volz , C , Mullen , W , Shirran , S L , Smith , B O , Kalinina , O V , Müller , R & Koehnke , J 2023 , ' Unusual peptide-binding proteins guide pyrroloindoline alkaloid formation in crocagin biosynthesis ' , Nature Chemistry , vol. 15 , no. 4 , pp. 560-568 . https://doi.org/10.1038/s41557-023-01153-wen
dc.identifier.issn1755-4330
dc.identifier.otherPURE: 283994958
dc.identifier.otherPURE UUID: e201bcb3-3de7-4e00-87b6-3b755c0323b9
dc.identifier.otherJisc: 1000566
dc.identifier.otherpublisher-id: s41557-023-01153-w
dc.identifier.othermanuscript: 1153
dc.identifier.otherScopus: 85149459257
dc.identifier.otherORCID: /0000-0003-3516-3507/work/132764188
dc.identifier.urihttps://hdl.handle.net/10023/27337
dc.descriptionFunding: This work was supported by the European Research Council (Consolidator Grant 101002326 to J.K.).en
dc.description.abstractRibosomally synthesized and post-translationally modified peptide natural products have provided many highly unusual scaffolds. This includes the intriguing alkaloids crocagins, which possess a tetracyclic core structure and whose biosynthesis has remained enigmatic. Here we use in vitro experiments to demonstrate that three proteins, CgnB, CgnC and CgnE, are sufficient for the production of the hallmark tetracyclic crocagin core from the precursor peptide CgnA. The crystal structures of the homologues CgnB and CgnE reveal them to be the founding members of a peptide-binding protein family and allow us to rationalize their distinct functions. We further show that the hydrolase CgnD liberates the crocagin core scaffold, which is subsequently N-methylated by CgnL. These insights allow us to propose a biosynthetic scheme for crocagins. Bioinformatic analyses based on these data led to the discovery of related biosynthetic pathways that may provide access to a structurally diverse family of peptide-derived pyrroloindoline alkaloids.
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofNature Chemistryen
dc.rightsCopyright © The Author(s) 2023.This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en
dc.subjectQD Chemistryen
dc.subjectDASen
dc.subjectMCCen
dc.subject.lccQDen
dc.titleUnusual peptide-binding proteins guide pyrroloindoline alkaloid formation in crocagin biosynthesisen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. Arctic Research Centreen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1038/s41557-023-01153-w
dc.description.statusPeer revieweden


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