IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37255-9.html
   My bibliography  Save this article

Self assembling nanoparticle enzyme clusters provide access to substrate channeling in multienzymatic cascades

Author

Listed:
  • Joyce C. Breger

    (U.S. Naval Research Laboratory)

  • James N. Vranish

    (U.S. Naval Research Laboratory
    Franciscan University of Steubenville)

  • Eunkeu Oh

    (U.S. Naval Research Laboratory)

  • Michael H. Stewart

    (U.S. Naval Research Laboratory)

  • Kimihiro Susumu

    (U.S. Naval Research Laboratory)

  • Guillermo Lasarte-Aragonés

    (U.S. Naval Research Laboratory
    George Mason University)

  • Gregory A. Ellis

    (U.S. Naval Research Laboratory)

  • Scott A. Walper

    (U.S. Naval Research Laboratory)

  • Sebastián A. Díaz

    (U.S. Naval Research Laboratory)

  • Shelby L. Hooe

    (U.S. Naval Research Laboratory
    National Research Council)

  • William P. Klein

    (U.S. Naval Research Laboratory
    National Research Council)

  • Meghna Thakur

    (U.S. Naval Research Laboratory
    George Mason University)

  • Mario G. Ancona

    (U.S. Naval Research Laboratory
    Florida State University)

  • Igor L. Medintz

    (U.S. Naval Research Laboratory)

Abstract

Access to efficient enzymatic channeling is desired for improving all manner of designer biocatalysis. We demonstrate that enzymes constituting a multistep cascade can self-assemble with nanoparticle scaffolds into nanoclusters that access substrate channeling and improve catalytic flux by orders of magnitude. Utilizing saccharification and glycolytic enzymes with quantum dots (QDs) as a model system, nanoclustered-cascades incorporating from 4 to 10 enzymatic steps are prototyped. Along with confirming channeling using classical experiments, its efficiency is enhanced several fold more by optimizing enzymatic stoichiometry with numerical simulations, switching from spherical QDs to 2-D planar nanoplatelets, and by ordering the enzyme assembly. Detailed analyses characterize assembly formation and clarify structure-function properties. For extended cascades with unfavorable kinetics, channeled activity is maintained by splitting at a critical step, purifying end-product from the upstream sub-cascade, and feeding it as a concentrated substrate to the downstream sub-cascade. Generalized applicability is verified by extending to assemblies incorporating other hard and soft nanoparticles. Such self-assembled biocatalytic nanoclusters offer many benefits towards enabling minimalist cell-free synthetic biology.

Suggested Citation

  • Joyce C. Breger & James N. Vranish & Eunkeu Oh & Michael H. Stewart & Kimihiro Susumu & Guillermo Lasarte-Aragonés & Gregory A. Ellis & Scott A. Walper & Sebastián A. Díaz & Shelby L. Hooe & William , 2023. "Self assembling nanoparticle enzyme clusters provide access to substrate channeling in multienzymatic cascades," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37255-9
    DOI: 10.1038/s41467-023-37255-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37255-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-37255-9?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
    ---><---

    References listed on IDEAS

    as
    1. Lee J. Sweetlove & Alisdair R. Fernie, 2018. "The role of dynamic enzyme assemblies and substrate channelling in metabolic regulation," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Yifei Zhang & Stanislav Tsitkov & Henry Hess, 2016. "Proximity does not contribute to activity enhancement in the glucose oxidase–horseradish peroxidase cascade," Nature Communications, Nature, vol. 7(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Alastair G. Kerr & Zuoneng Wang & Na Wang & Kelvin H. M. Kwok & Jutta Jalkanen & Alison Ludzki & Simon Lecoutre & Dominique Langin & Martin O. Bergo & Ingrid Dahlman & Carsten Mim & Peter Arner & Hui , 2022. "The long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. György Abrusán & Aleksej Zelezniak, 2024. "Cellular location shapes quaternary structure of enzymes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Weronika Jasinska & Mirco Dindo & Sandra M. C. Cordoba & Adrian W. R. Serohijos & Paola Laurino & Yariv Brotman & Shimon Bershtein, 2024. "Non-consecutive enzyme interactions within TCA cycle supramolecular assembly regulate carbon-nitrogen metabolism," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Prabhu Dhasaiyan & Tanwistha Ghosh & Hong-Guen Lee & Yeonsang Lee & Ilha Hwang & Rahul Dev Mukhopadhyay & Kyeng Min Park & Seungwon Shin & In Seok Kang & Kimoon Kim, 2022. "Cascade reaction networks within audible sound induced transient domains in a solution," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Liangxiao Tan & Jun-Hao Zhou & Jian-Ke Sun & Jiayin Yuan, 2022. "Electrostatically cooperative host-in-host of metal cluster ⊂ ionic organic cages in nanopores for enhanced catalysis," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    6. Xixi Sun & Yujie Yuan & Qitong Chen & Shiqi Nie & Jiaxuan Guo & Zutian Ou & Min Huang & Zixin Deng & Tiangang Liu & Tian Ma, 2022. "Metabolic pathway assembly using docking domains from type I cis-AT polyketide synthases," Nature Communications, Nature, vol. 13(1), pages 1-12, 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:14:y:2023:i:1:d:10.1038_s41467-023-37255-9. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.