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Nanoscale Enzymatic Compartments in Tandem Support Cascade Reactions in Vitro

Belluati, Andrea and Craciun, Ioana and Liu, Juan and Palivan, Cornelia G.. (2018) Nanoscale Enzymatic Compartments in Tandem Support Cascade Reactions in Vitro. Biomacromolecules, 19 (10). pp. 4023-4033.

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Official URL: https://edoc.unibas.ch/67886/

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Abstract

Compartmentalization at the nanoscale is fundamental in nature, where the spatial segregation of biochemical reactions within cells ensures optimal conditions for regulating metabolic pathways. Here, we present a nature-inspired approach to engineer enzymatic cascade reactions taking place between separate vesicular nanocompartments (polymersomes), each containing one enzyme type. We propose, by the selected combination of enzymes, an efficient solution to detoxify the harmful effect of uric acid and prevent the accumulation of the derived H2O2, both being associated with various pathological conditions (e.g., gout and oxidative stress). Fungal uricase and horseradish peroxidase combined to act in tandem, and they were separately encapsulated within nanocompartments that were equipped with channel porins as gates to allow passage of substrates and products from each step of the reaction. We established the molecular factors affecting the efficiency of the overall reaction, and the protective role of the compartments. Interestingly, the cascade reaction between separate nanocompartments was as efficient as for free enzymes in complex media, such as human serum. The nanocompartments were nontoxic toward cells, and more importantly, addition of the tandem catalytic nanocompartments to cells exposed to uric acid provided simultaneous detoxification of uric acid and the H2O2. Such catalytic nanocompartments can be used as a platform for understanding fundamental factors affecting intracellular communication and can introduce non-native metabolic reactions into living systems for therapeutic applications.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Makromolekulare Chemie (Meier)
05 Faculty of Science > Departement Chemie > Chemie > Physikalische Chemie (Palivan)
UniBasel Contributors:Palivan, Cornelia G
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
ISSN:1525-7797
e-ISSN:1526-4602
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:06 Feb 2019 14:18
Deposited On:06 Feb 2019 14:18

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