Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion

Zhao Zhao, Jinglin Fu, Soma Dhakal, Alexander Johnson-Buck, Minghui Liu, Ting Zhang, Neal W. Woodbury, Yan Liu, Nils G. Walter, Hao Yan

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology.

Original languageEnglish
Article number10619
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Feb 10 2016

Fingerprint

protease
catalytic activity
enzymes
Digestion
Catalyst activity
Peptide Hydrolases
Enzymes
deoxyribonucleic acid
DNA
Enzyme Stability
Biocompatible Materials
biotechnology
Biotechnology
Metabolic Networks and Pathways
Encapsulation
Stoichiometry
Hydration
Self assembly
hydration
Conformations

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion. / Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W.; Liu, Yan; Walter, Nils G.; Yan, Hao.

In: Nature Communications, Vol. 7, 10619, 10.02.2016.

Research output: Contribution to journalArticle

Zhao, Zhao ; Fu, Jinglin ; Dhakal, Soma ; Johnson-Buck, Alexander ; Liu, Minghui ; Zhang, Ting ; Woodbury, Neal W. ; Liu, Yan ; Walter, Nils G. ; Yan, Hao. / Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion. In: Nature Communications. 2016 ; Vol. 7.
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