Directional Regulation of Enzyme Pathways through the Control of Substrate Channeling on a DNA Origami Scaffold

Ke, Guoliang; Liu, Minghui; Jiang, Shuoxing; Qi, Xiaodong; Yang, Yuhe; Wootten, Shaun; Zhang, Fei; Zhu, Zhi; Liu, Yan; Yang, Chaoyong; Yan, Hao

doi:10.1002/anie.201603183

Cited by 131 publications

(123 citation statements)

References 32 publications

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“…Besides one‐directional substrate transport by multienzyme complexes along a single enzymatic pathway, precise and dynamic control over multiple pathways would be interesting. One such example of switching between two different enzymatic pathways was reported recently for the G6pDH/MDH and G6pDH/LDH enzyme pairs . The enzymatic reactions tested for G6pDH and MDH are exactly the same as described above in Section 4.1, whereas LDH converts pyruvate into lactate in the presence of NADH.…”

Section: Scaffolded Dna Origami Templatesmentioning

confidence: 80%

“…By increasingt he relative proportion of MDH, it is possible to enhance the efficiency and the rates of associated cascade reactions, as demonstratedb yF ue tal. [15] To mimic the multienzyme complexes of living cells, enzymesa re often immobilized on carriers.A mong the various approaches (such as using protein [16][17][18][19] and lipid bilayer [20] templates) for the development of artificial enzyme cascade systems, nucleic acids and their nanostructures have recently been applied to achieve particulars patialo rganizationso f enzymes to form metabolons that transfer the substrates between one another.T he common DNA templates used so far are duplex DNA (dsDNA), either in bulk solution [21] or immobilized onto the surfaceo famicroplate [22,23] or an electrode, [24] aptamer-domain-containing DNAs, [25,26] Y-shaped DNA, [27] long DNA chains prepared by the rolling circle amplification (RCA) process, [28] hexagon-like DNA strips, [29] DNA double-crossover (DX) tiles, [15] tuneable DNA tweezers made of DNA DX motifs, [30] three-point star DNA scaffoldsa nd scaffoldedD NA origami [31] with 2D structures, [10,14,[32][33][34] as well as 3D tubes [32,35] and nanocages. [36] Although these DNA-templated enzyme cascade reactions are limited to in vitro studies, they provide ideal systemsf or exploring the chemistry behind cellular enzyme cascade reactions.…”

Section: Introductionmentioning

confidence: 99%

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Nucleic‐Acid‐Templated Enzyme Cascades

et al. 2017

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Cellular metabolism involves complex sequences of organized enzymatic reactions, known as metabolic pathways, that convert substrates into readily usable materials. In nature, these enzymatic complexes are organized in a well-defined manner so that the cascade reactions are more rapid and efficient than they would be if the enzymes were randomly distributed in the cytosol. Development of artificial enzyme cascades that resemble nature's organization of sequentially assembled enzymes is of current interest due to its potential applications, from diagnostics to the production of high-value chemicals. Nucleic acids and their nanostructures have been used to organize enzyme cascades and have been shown to enhance the efficiencies and rates of sequential reactions. Here we summarize the recent progress in the development of artificial enzyme cascades and sequential reactions by arranging enzymes on various DNA/RNA templates and discuss the future directions of this research endeavour.

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Section: Scaffolded Dna Origami Templatesmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Nucleic‐Acid‐Templated Enzyme Cascades

et al. 2017

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“…10d, the reaction specificity of the G6PDH-MDH cascade was also increased in the presence of a competing enzyme of lactate dehydrogenase (LDH). NAD + -modified DNA arms have also been successfully used to regulate the pathway direction between G6PDH-MDH and G6PDH-LDH [123], with the directional regulation of enzyme pathways controlled by DNA strand displacement [123] or the photo-responsive reaction (Fig. 11a) [124].…”

Section: Biomimetic Assembly Of Macromolecular Complexesmentioning

confidence: 99%

DNA-Scaffolded Proximity Assembly and Confinement of Multienzyme Reactions

Wang

Liang

et al. 2020

Top Curr Chem (Z)

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Cellular functions rely on a series of organized and regulated multienzyme cascade reactions. The catalytic efficiencies of these cascades depend on the precise spatial organization of the constituent enzymes, which is optimized to facilitate substrate transport and regulate activities. Mimicry of this organization in a non-living, artificial system would be very useful in a broad range of applications-with impacts on both the scientific community and society at large. Self-assembled DNA nanostructures are promising applications to organize biomolecular components into prescribed, multidimensional patterns. In this review, we focus on recent progress in the field of DNA-scaffolded assembly and confinement of multienzyme reactions. DNA self-assembly is exploited to build spatially organized multienzyme cascades with control over their relative distance, substrate diffusion paths, compartmentalization and activity actuation. The combination of addressable DNA assembly and multienzyme cascades can deliver breakthroughs toward the engineering of novel synthetic and biomimetic reactors.

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“…GOx: glucose oxidase, HRP: horseradish peroxidase, ABTS: 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid. D) Directional regulation of enzyme pathways through the control of substrate channeling on a DNA origami scaffold . G6pDH: glucose‐6‐phosphate dehydrogenase, LDH: lactate dehydrogenase, MDH: malate dehydrogenase.…”

Section: Directed Assembly Of Soluble Proteins On Dna Origamimentioning

confidence: 99%

DNA Origami as Scaffolds for Self‐Assembly of Lipids and Proteins

Dong

Mao

2019

ChemBioChem

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Since first being reported in 2006, the DNA origami approach has attracted increasing attention due to programmable shapes, structural stability, biocompatibility, and fantastic addressability. Herein, we provide an account of recent developments of DNA origami as scaffolds for templating the selfassembly of distinct biocomponents, essentially proteins and lipids, into a diverse spectrum of integrated supramolecular architectures. First, the historical development of the DNA origami concept is briefly reviewed. Next, various applications of DNA origami constructs in controllable directed assembly of soluble proteins are discussed. The manipulation and self‐assembly of lipid membranes and membrane proteins by using DNA origami as scaffolds are also addressed. Furthermore, recent progress in applying DNA origami in cryoelectron microscopy analysis is discussed. These advances collectively emphasize that the DNA origami approach is a highly versatile, fast evolving tool that may be integrated with lipids and proteins in a way that meets future challenges in molecular biology and nanomedicine.

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Directional Regulation of Enzyme Pathways through the Control of Substrate Channeling on a DNA Origami Scaffold

Cited by 131 publications

References 32 publications

Nucleic‐Acid‐Templated Enzyme Cascades

Nucleic‐Acid‐Templated Enzyme Cascades

DNA-Scaffolded Proximity Assembly and Confinement of Multienzyme Reactions

DNA Origami as Scaffolds for Self‐Assembly of Lipids and Proteins

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