IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-06325-8.html
   My bibliography  Save this article

Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis

Author

Listed:
  • Ronja Driller

    (Freie Universität Berlin)

  • Sophie Janke

    (Freie Universität Berlin)

  • Monika Fuchs

    (Technical University of Munich (TUM))

  • Evelyn Warner

    (Freie Universität Berlin)

  • Anil R. Mhashal

    (Bar-Ilan University)

  • Dan Thomas Major

    (Bar-Ilan University)

  • Mathias Christmann

    (Freie Universität Berlin)

  • Thomas Brück

    (Technical University of Munich (TUM))

  • Bernhard Loll

    (Freie Universität Berlin)

Abstract

Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C–C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation intermediates through an enzyme-specific reaction. Due to the instability of carbocation intermediates, the proteins’ structural dynamics and enzyme:substrate interactions during TPS catalysis remain elusive. Here, we present the structure of the diterpene synthase CotB2, in complex with an in crystallo cyclised abrupt reaction product and a substrate-derived diphosphate. We captured additional snapshots of the reaction to gain an overview of CotB2’s catalytic mechanism. To enhance insights into catalysis, structural information is augmented with multiscale molecular dynamic simulations. Our data represent fundamental TPS structure dynamics during catalysis, which ultimately enable rational engineering towards tailored terpene macrocycles that are inaccessible by conventional chemical synthesis.

Suggested Citation

  • Ronja Driller & Sophie Janke & Monika Fuchs & Evelyn Warner & Anil R. Mhashal & Dan Thomas Major & Mathias Christmann & Thomas Brück & Bernhard Loll, 2018. "Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06325-8
    DOI: 10.1038/s41467-018-06325-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-06325-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-018-06325-8?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
    ---><---

    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:9:y:2018:i:1:d:10.1038_s41467-018-06325-8. 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.