Structural and evolutionary analyses support reclassification of glycopeptide antibiotics as xyclopeptides

Structural and evolutionary analyses support reclassification of glycopeptide antibiotics as xyclopeptides | bioRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Structural and evolutionary analyses support reclassification of glycopeptide antibiotics as xyclopeptides View ORCID Profile Athina Gavriilidou , View ORCID Profile Noel Kubach , View ORCID Profile Martina Adamek , Jens-Peter Rodler , Susanna Kremer , View ORCID Profile Daniel H. Huson , View ORCID Profile Rosa Alduina , View ORCID Profile Gerard Wright , View ORCID Profile Mohammad Seyemsayadost , View ORCID Profile Wolfgang Wohlleben , View ORCID Profile Stefano Donadio , View ORCID Profile Margherita Sosio , View ORCID Profile Min Xu , View ORCID Profile Max J. Cryle , Evi Stegmann , View ORCID Profile Nadine Ziemert doi: https://doi.org/10.1101/2023.02.10.526856 Athina Gavriilidou 1 Translational Genome Mining for Natural Products, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), Interfaculty Institute for Biomedical Informatics (IBMI), University of Tübingen , Tübingen, Germany / Cluster of Excellence ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen , Tübingen, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Athina Gavriilidou Noel Kubach 1 Translational Genome Mining for Natural Products, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), Interfaculty Institute for Biomedical Informatics (IBMI), University of Tübingen , Tübingen, Germany / Cluster of Excellence ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen , Tübingen, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Noel Kubach Martina Adamek 1 Translational Genome Mining for Natural Products, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), Interfaculty Institute for Biomedical Informatics (IBMI), University of Tübingen , Tübingen, Germany / Cluster of Excellence ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen , Tübingen, Germany 2 German Centre for Infection Research (DZIF) , Partnersite Tübingen, Tübingen, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Martina Adamek Jens-Peter Rodler 3 Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen , Auf der Morgenstelle 28, 72076 Tübingen, Germany / Cluster of Excellence ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen , Tübingen, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site Susanna Kremer 1 Translational Genome Mining for Natural Products, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), Interfaculty Institute for Biomedical Informatics (IBMI), University of Tübingen , Tübingen, Germany / Cluster of Excellence ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen , Tübingen, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site Daniel H. Huson 4 Algorithms in Bioinformatics, Computer Science Department, University of Tübingen , Tübingen, 72076, Germany , Interfaculty Institute for Biomedical Informatics (IBMI), University of Tübingen , Tübingen, Germany / Cluster of Excellence ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen , Tübingen / Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Daniel H. Huson Rosa Alduina 5 Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo , 90128 Palermo, Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Rosa Alduina Gerard Wright 6 Department of Biochemistry & Biomedical Sciences, David Braley Center for Antibiotic Discovery, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University , Hamilton, Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Gerard Wright Mohammad Seyemsayadost 7 Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mohammad Seyemsayadost Wolfgang Wohlleben 8 Microbiology/Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen , Auf der Morgenstelle 28, 72076 Tübingen, Germany / Cluster of Excellence ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen , Tübingen, Germany 2 German Centre for Infection Research (DZIF) , Partnersite Tübingen, Tübingen, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Wolfgang Wohlleben Stefano Donadio 9 Naicons Srl , Milan, Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Stefano Donadio Margherita Sosio 9 Naicons Srl , Milan, Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Margherita Sosio Min Xu 10 National Technology Innovation Center of Synthetic Biology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences , Tianjin 300308, China 11 Haihe Laboratory of Synthetic Biology , Tianjin 300308, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Min Xu Max J. Cryle 12 Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute, Monash University , Clayton, VIC, 3800, Australia 13 ARC Centre of Excellence for Innovations in Peptide and Protein Science , Clayton, Victoria 3800, Australia Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Max J. Cryle Evi Stegmann 2 German Centre for Infection Research (DZIF) , Partnersite Tübingen, Tübingen, Germany 3 Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen , Auf der Morgenstelle 28, 72076 Tübingen, Germany / Cluster of Excellence ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen , Tübingen, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: nadine.ziemert{at}uni-tuebingen.de Nadine Ziemert 1 Translational Genome Mining for Natural Products, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), Interfaculty Institute for Biomedical Informatics (IBMI), University of Tübingen , Tübingen, Germany / Cluster of Excellence ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen , Tübingen, Germany 2 German Centre for Infection Research (DZIF) , Partnersite Tübingen, Tübingen, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Nadine Ziemert For correspondence: nadine.ziemert{at}uni-tuebingen.de Abstract Full Text Info/History Metrics Supplementary material Preview PDF Abstract Glycopeptide antibiotics (GPAs) are key agents against multidrug-resistant Gram-positive pathogens, yet both the term “glycopeptide” and the current GPA type I-V classification framework have become increasingly strained as structurally and mechanistically divergent members continue to be discovered. In particular, compounds historically grouped as “type V GPAs” differ from classical GPAs in features such as glycosylation, peptide length, and reported mode of action, raising the question of whether they belong to the same natural product class. Here, a curated dataset of GPA-associated biosynthetic gene clusters (BGCs) is analysed by combining fingerprint similarity of the products with phylogenetic analysis of the BGCs. Fingerprint-based structural similarity networks and BGC similarity comparisons reveal a pronounced separation between classical lipid II-binding GPAs (types I-IV) and type V GPAs. Multi-locus phylogenetic analyses of conserved biosynthetic components further support two deeply divergent evolutionary subclasses, consistent with subclass-specific biosynthetic signatures. Together, these results motivate a revised, unambiguous framework in which the broader class is termed xyclopeptides, comprising the subclasses dalabactins (legacy GPA types I–IV) and murobactins (legacy type V). Competing Interest Statement The authors have declared no competing interest. Footnotes Complete restructuring of the manuscript with extended dataset and clearly defined nomenclature. Funder Information Declared Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64 , 398967434-TRR 261 German Center for Infection Research , TTU 09.716 Germany’s Excellence Strategy , EXC 2124-390838134 Joint Programming Initiative on Antimicrobial Resistance , AVOGADRO Bundesministerium für Forschung, Technologie und Raumfahrt , 01KI2503 Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science , CE200100012 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted April 06, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Structural and evolutionary analyses support reclassification of glycopeptide antibiotics as xyclopeptides Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Structural and evolutionary analyses support reclassification of glycopeptide antibiotics as xyclopeptides Athina Gavriilidou , Noel Kubach , Martina Adamek , Jens-Peter Rodler , Susanna Kremer , Daniel H. Huson , Rosa Alduina , Gerard Wright , Mohammad Seyemsayadost , Wolfgang Wohlleben , Stefano Donadio , Margherita Sosio , Min Xu , Max J. Cryle , Evi Stegmann , Nadine Ziemert bioRxiv 2023.02.10.526856; doi: https://doi.org/10.1101/2023.02.10.526856 Share This Article: Copy Citation Tools Structural and evolutionary analyses support reclassification of glycopeptide antibiotics as xyclopeptides Athina Gavriilidou , Noel Kubach , Martina Adamek , Jens-Peter Rodler , Susanna Kremer , Daniel H. Huson , Rosa Alduina , Gerard Wright , Mohammad Seyemsayadost , Wolfgang Wohlleben , Stefano Donadio , Margherita Sosio , Min Xu , Max J. Cryle , Evi Stegmann , Nadine Ziemert bioRxiv 2023.02.10.526856; doi: https://doi.org/10.1101/2023.02.10.526856 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Genetics Subject Areas All Articles Animal Behavior and Cognition (8003) Biochemistry (18709) Bioengineering (14841) Bioinformatics (44364) Biophysics (22561) Cancer Biology (19682) Cell Biology (26845) Clinical Trials (138) Developmental Biology (13943) Ecology (20970) Epidemiology (2067) Evolutionary Biology (25415) Genetics (16151) Genomics (23478) Immunology (18681) Microbiology (42421) Molecular Biology (18022) Neuroscience (93355) Paleontology (699) Pathology (2977) Pharmacology and Toxicology (5086) Physiology (8105) Plant Biology (15969) Scientific Communication and Education (2094) Synthetic Biology (4549) Systems Biology (10219) Zoology (2384)

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