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

Introduction

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.

Enzymatic Activity in Nature

In nature, enzymatic activity and efficiency are often enhanced by encapsulation of enzymes in microcompartments. This encapsulation results in protection and rate enhancement through high local concentrations of enzymes, co-factors, and substrates.

Project Overview

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.

Advantages of DNA Origami

These inorganic materials retain the attractive features of DNA origami, such as:

• Precise localization
• 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.

Addressing Global Challenges

NanoCat is a novel approach to assemble complex enzymes outside of their natural environments to address:

1. Health issues
2. Global carbon emissions
3. Plant fertilizers

These are areas where current biological methods struggle to provide effective solutions.

Urgent Demand for Engineered Systems

The immense demand in today’s agricultural, climate, and health needs urgently calls for engineered systems with full control over:

• Size
• Shape
• Functionalizability

This control is essential to enhance enzymatic activity and endow organisms with new and improved properties.

Conclusion

NanoCat aims to provide a solution to these issues through the assembly of artificial enzyme-hosting microcompartments from silicified DNA origami with universal applicability. I will exemplify this through the formation of “carboxy-, nitrogy- and galactysomes” for CO2/nitrogen fixation and the cellular delivery of essential lysosomal enzymes.