DNA-Scaffolded Proximity Assembly and Confinement of Multienzyme Reactions
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DNA‑Scaffolded Proximity Assembly and Confinement of Multienzyme Reactions Jinglin Fu1,2 · Zhicheng Wang1,2 · Xiao Hua Liang1 · Sung Won Oh2 · Ezry St. Iago‑McRae2 · Ting Zhang1 Received: 21 October 2019 / Accepted: 7 March 2020 © Springer Nature Switzerland AG 2020
Abstract 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. Keywords Biomimetic systems · DNA nanotechnology · DNA scaffolded assembly · Enzyme encapsulation · Enzyme immobilization · Enzyme regulation · Multienzyme cascade · Synthetic reactors Abbreviations BG Benzylguanine BQ Benzoquinone This article is part of the Topical Collection “DNA Nanotechnology: From Structure to Functionality”; edited by Chunhai Fan, Yonggang Ke. * Jinglin Fu [email protected] 1
Department of Chemistry, Rutgers University–Camden, Camden, NJ 08102, USA
2
Center for Computational and Integrative Biology, Rutgers University–Camden, Camden, NJ 08102, USA
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Topics in Current Chemistry
(2020) 378:38
CH Chlorohexane DSS Disuccinimidyl suberate DTPC DNA-templated protein conjugation DX Double-crossover DNA tile G6PDH Glucose-6-phosphate dehydrogenase GOx Glucose oxidase HRP Horseradish peroxidase IDE Inhibitor–DNA–enzyme LDH Lactate dehydrogenase MDH Malic dehydrogenase MTG Microbial transglutaminase NHS N-hydroxysuccinimide NiR Nitrite reductase ORBIT Origami-rotor-based imaging and tracking Paz Pseudoazurin Pg Plasminogen PLP Pyridoxal 5′-phosphate SK Streptokinase SMCC Succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate SPDP Succinimidyl 3-(2-pyridyldithio) propionate STVs Streptavidins TAL Transcription activator-like
1 Introduction Multistep enzyme pathways play critical roles in cellular metabolism that produces biomolecules and harvests energy for sustaining and propagating living systems. As of 2019, 7727 different enzymes have been recorded in the BRENDA database, a comprehensive enzyme information system, including enzymes found in human cells and bac
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