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Updated: Jun 13, 2026

Synthesis of Stimuli-responsive Nanogels using Aqueous One-step Crosslinking and Co-nanopolymerization
Published on: January 24, 2025
Oppositely Charged Single Enzyme Nanogels Form Versatile Coacervates for Efficient Enzyme Cascade Catalysis
Andoni Rodriguez-Abetxuko1, Nadia A Erkamp1, Neshat Moslehi1
1Department of Chemical Engineering and Chemistry and Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, The Netherlands.
Abstract:
Enzymatic cascade systems enhance the efficiency of biocatalysis by mimicking natural metabolic pathways. However, conventional platforms face challenges such as ineffective enzyme distribution, uncontrolled stoichiometry, limited substrate accessibility, and a microenvironment that is suboptimal for enzyme performance. Inspired by cellular biomolecular condensates, we here present a design based on oppositely charged single enzyme nanogels (SENs) that phase separate into denser microdroplet coacervates, which thereby serve both as an immobilization scaffold and functional unit. These coacervates, the first fabricated exclusively from oppositely charged nanogels, form under broad environmental conditions and enable specific microenvironments by adjusting SEN ratios to match the requirements of coupled enzymes. Selective substrate enrichment and efficient diffusion of intermediates enhance cascade productivity. The applicability of the platform is demonstrated with pharmaceutically relevant enzymes, highlighting its potential for biosynthetic applications. This work establishes a new paradigm that integrates protein-polymer engineering with phase separation chemistry to overcome key limitations in cascade enzyme catalysis.
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