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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
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    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)

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