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From CO2 and Nitrogen fixation to the delivery of therapeutic enzymes: Silicified DNA origami as artificial microcompartments

Project description

Silica ‘bubble’ hosts engineered enzyme cascades, improving their efficiency

Enzymes are nature’s catalysts, essential to life and health and playing important roles in disease. Their function depends on how well the enzymes are protected as well as on other molecules, including co-factors and their substrates, with which they bind. Ensuring that these molecules are in proximity so that the enzymes can do their work efficiently and safe from detrimental factors is often accomplished in nature by encapsulation. To enhance the activity and effectiveness of multi-enzyme systems, the ERC-funded NanoCat project aims to engineer artificial microcompartments containing all the ingredients for highly efficient enzyme cascades that are operational in organisms where they do not naturally occur. The solution will leverage biocompatible silica to encapsulate the DNA origami hosting the enzymes.

Objective

All life is dependent on enzymatic reactions and functional enzyme cascades have been evolutionary optimized. Yet, introducing “foreign” enzymes into other organisms through genetic engineering often results in reduced or no enzymatic activity. In nature enzymatic activity and efficiency are often enhanced by encapsulation of enzymes in microcompartments resulting in protection and rate enhancement through high local concentrations of enzymes, co-factors and substrates. In NanoCat I will engineer artificial microcompartments hosting highly efficient enzyme cascades that are operational in organisms where they do not naturally occur. The approach is based on my recently developed method to controllably template silica nanostructures by DNA origami. These inorganic materials retain the attractive features of DNA origami like precise localization and number placement of proteins of interest. Combining the power of DNA nanotechnology with the sturdiness and biocompatibility of silica as artificial enzyme-hosting microcompartments, I now have a highly disruptive tool at hand that has the power to outperform standard biological methods and be a true game changer. NanoCat is a novel approach to assemble complex enzymes outside of their natural environments to address health issues, global carbon emissions and plant fertilizers, something that current biological methods struggle to do. The immense demand in today’s agricultural, climate and health needs urgently calls for engineered systems with full control over size, shape and functionalizability to enhance enzymatic activity and endow organisms with new and improved properties. NanoCat aims to provide a solution to these issues through the assembly of artificial enzyme-hosting microcompartments from silicified DNA origami with universal applicability, which I will exemplify through the formation of “carboxy-, nitrogy- and galactysomes” for CO2/nitrogen fixation and the cellular delivery of essential lysosomal enzymes.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2023-COG

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Host institution

TECHNISCHE UNIVERSITAT DORTMUND
Net EU contribution
€ 1 916 142,50
Address
AUGUST SCHMIDT STRASSE 4
44227 Dortmund
Germany
Region
Nordrhein-Westfalen Arnsberg Dortmund, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 916 142,50

Beneficiaries (2)