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

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.