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Explore DNA Nanostructures for Controlling Multienzyme Assembly and Modulating Catalysis

ORAL · Invited

Abstract

Cellular functions rely on a series of organized and regulated multienzyme cascade reactions. The catalytic efficiency of multienzyme complexes depends on the spatial organization of composite components which are precisely controlled to facilitate substrate transport and regulate activities. If these cellular mechanisms can be mimicked and translated to a non-living artificial system, it can be useful in a broad range of applications that will bring significant scientific and economic impact. Self-assembled DNA nanostructures are promising to organize biomolecular components into prescribed, multi-dimensional patterns. Here, we described a robust strategy for DNA-scaffolded assembly and confinement of biochemical reactions. DNA nanostructures are used to organize spatial arrangements of multienzyme cascades with control over their relative distance, substrate channeling paths, compartmentalization, local confinement of ligands, as well as the construction of smart and biomimetic reactors. The combination of addressable DNA assembly and multienzyme cascades promises to deliver breakthroughs toward the engineering of novel biomimetic nanomaterials, which have great potential for broad applications from chemical synthesis, functional biomaterials and biofuel production to therapeutics and diagnosis.

Publication: 1. Zhicheng Wang, Ezry St. Iago-Mcrae, Alireza Ebrahimimojarad, Sung Won Oh and Jinglin Fu* "Modulation of Enzyme Cascade Activity by Local Substrate Enrichment and Exclusion on DNA Nanostructures" Langmuir 2022. https://doi.org/10.1021/acs.langmuir.2c02064 <br>2. Jinglin Fu*, Zhicheng Wang, Xiaohua Anna Liang, Sung Won Oh and Ting Zhang "DNA-Scaffolded Proximity Assembly and Confinement of Multienzyme Reactions" Topics in Current Chemistry 2020, published online, DOI: 10.1007/s41061-020-0299-3.<br>3. Jinglin Fu*, Sung Won Oh, Kristin Monckton, Georgia Arbuckle-Keil, Yonggang Ke and Ting Zhang "Biomimetic Compartments Scaffolded by Nucleic Acid Nanostructures" Small 2019, 1900256. https://doi.org/10.1002/smll.201900256. <br>4. John Collins, Ting Zhang, Sung Won Oh, Robert Maloney and Jinglin Fu* "DNA-Crowded Enzyme Complexes with Enhanced Activities and Stabilities", Chem Comm. 2017, 53, 13059–13062.<br>5. Jinglin Fu*, Renee Yang, Soma Dhakal, Zhao Zhao, Minghui Liu, Ting Zhang, Nils Walter and Hao Yan "Assembly of Multi-Enzyme Complexes on DNA Nanostructures", Nature Protocols 2016, 11,2243–2273.<br>6. Jinglin Fu*, Yuhe Renee Yang, Alexander Johnson-Buck, Minghui Liu, Yan Liu, Nils G. Walter, Neal W. Woodbury and Hao Yan* "Multi-enzyme complexes on DNA scaffolds capable of substrate channeling with an artificial swinging arm" Nature Nanotechnology 2014, 9, 531–536.<br>7. Jinglin Fu, Minghui Liu, Yan Liu, Neal Woodbury and Hao Yan* "Inter-enzyme Substrate Diffusion for An Enzyme Cascade Organized on Spatially Addressable DNA Nanostructures", Journal of American Chemical Society 2012, 134, 5516-5519.

Presenters

  • Jinglin Fu

    Rutgers University-Camden

Authors

  • Jinglin Fu

    Rutgers University-Camden