IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-10384-w.html
   My bibliography  Save this article

Kistamicin biosynthesis reveals the biosynthetic requirements for production of highly crosslinked glycopeptide antibiotics

Author

Listed:
  • Anja Greule

    (The Monash Biomedicine Discovery Institute, Monash University
    EMBL Australia, Monash University)

  • Thierry Izoré

    (The Monash Biomedicine Discovery Institute, Monash University
    EMBL Australia, Monash University)

  • Dumitrita Iftime

    (University of Tübingen)

  • Julien Tailhades

    (The Monash Biomedicine Discovery Institute, Monash University
    EMBL Australia, Monash University)

  • Melanie Schoppet

    (The Monash Biomedicine Discovery Institute, Monash University
    EMBL Australia, Monash University)

  • Yongwei Zhao

    (The Monash Biomedicine Discovery Institute, Monash University
    EMBL Australia, Monash University)

  • Madeleine Peschke

    (Max Planck Institute for Medical Research)

  • Iftekhar Ahmed

    (The University of Queensland)

  • Andreas Kulik

    (University of Tübingen)

  • Martina Adamek

    (University of Tübingen)

  • Robert J. A. Goode

    (The Monash Biomedicine Discovery Institute, Monash University
    Monash University)

  • Ralf B. Schittenhelm

    (The Monash Biomedicine Discovery Institute, Monash University
    Monash University)

  • Joe A. Kaczmarski

    (The Australian National University)

  • Colin J. Jackson

    (The Australian National University)

  • Nadine Ziemert

    (University of Tübingen)

  • Elizabeth H. Krenske

    (The University of Queensland)

  • James J. Voss

    (The University of Queensland)

  • Evi Stegmann

    (University of Tübingen
    German Centre for Infection Research (DZIF), Partner Site Tübingen)

  • Max J. Cryle

    (The Monash Biomedicine Discovery Institute, Monash University
    EMBL Australia, Monash University)

Abstract

Kistamicin is a divergent member of the glycopeptide antibiotics, a structurally complex class of important, clinically relevant antibiotics often used as the last resort against resistant bacteria. The extensively crosslinked structure of these antibiotics that is essential for their activity makes their chemical synthesis highly challenging and limits their production to bacterial fermentation. Kistamicin contains three crosslinks, including an unusual 15-membered A-O-B ring, despite the presence of only two Cytochrome P450 Oxy enzymes thought to catalyse formation of such crosslinks within the biosynthetic gene cluster. In this study, we characterise the kistamicin cyclisation pathway, showing that the two Oxy enzymes are responsible for these crosslinks within kistamicin and that they function through interactions with the X-domain, unique to glycopeptide antibiotic biosynthesis. We also show that the kistamicin OxyC enzyme is a promiscuous biocatalyst, able to install multiple crosslinks into peptides containing phenolic amino acids.

Suggested Citation

  • Anja Greule & Thierry Izoré & Dumitrita Iftime & Julien Tailhades & Melanie Schoppet & Yongwei Zhao & Madeleine Peschke & Iftekhar Ahmed & Andreas Kulik & Martina Adamek & Robert J. A. Goode & Ralf B., 2019. "Kistamicin biosynthesis reveals the biosynthetic requirements for production of highly crosslinked glycopeptide antibiotics," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10384-w
    DOI: 10.1038/s41467-019-10384-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-10384-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-10384-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Mathias H. Hansen & Martina Adamek & Dumitrita Iftime & Daniel Petras & Frauke Schuseil & Stephanie Grond & Evi Stegmann & Max J. Cryle & Nadine Ziemert, 2023. "Resurrecting ancestral antibiotics: unveiling the origins of modern lipid II targeting glycopeptides," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10384-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.