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Biocatalytic cascades operating on macromolecular scaffolds and in confined environments

Nature Catalysis volume 3, pages 256–273 (2020)Cite this article

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Abstract

Biocatalytic cascades guide complex, efficient and selective intracellular transformations. These unique features originate from the spatial organization of the biocatalysts in confined cellular environments that allow the directional channelling of reaction intermediates across the cells. Here we address efforts directed towards the development of synthetic cell analogues and supramolecular ensembles acting as nano/microenvironments for operating biocatalytic cascades. Multienzyme systems are integrated within metal–organic frameworks, polymersomes, lipid-stabilized microdroplets and hydrogel microparticles acting as cell-like containments. Also, multienzyme systems are spatially positioned on one-dimensional DNA wires, two-dimensional DNA strips or origami tiles, and three-dimensional DNA origami bundles or cages, and specific protein–protein interactions or peptide–protein complexes provide versatile scaffolds for engineering enzyme assemblies. Biocatalytic cascades operating on these scaffolds or in confined nano/microenvironments reveal substantially enhanced reaction yields compared with the analogous diffusional mixtures of the biocomponents. Mechanistic pathways accounting for the enhanced biocatalytic activities and future challenges in developing and applying biocatalytic cascades are presented.

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Fig. 1: Biocatalytic cascades in organized nano/microenvironments.
Fig. 2: Multienzyme cascades in MOF nanoparticles.
Fig. 3: Biocatalytic cascades driven in micro- and nanosized containments.
Fig. 4: Spatially controlled biocatalytic cascades operating on programmed nucleic acid scaffolds.
Fig. 5: Operation of biocatalytic cascades using 3D DNA scaffolds.
Fig. 6: Switching enzyme cascades in the presence of DNA nanostructures.
Fig. 7: Operation of biocatalytic cascades on protein scaffolds.
Fig. 8: Schematic presentation of reaction-intermediate channelling pathways in scaffolded bienzyme cascades.

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Acknowledgements

Our research on biocatalytic transformations on confined media is supported by the Volkswagen Foundation, Germany.

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  1. These authors contributed equally: Margarita Vázquez-González, Chen Wang.

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  1. Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

    Margarita Vázquez-González, Chen Wang & Itamar Willner

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Vázquez-González, M., Wang, C. & Willner, I. Biocatalytic cascades operating on macromolecular scaffolds and in confined environments. Nat Catal 3, 256–273 (2020). https://doi.org/10.1038/s41929-020-0433-1

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