Enzyme Mimicking by Metabolite-Metal Nanozymes with Exceptional Operational Stability

Descripción del proyecto

Enzimas para una gran variedad de aplicaciones

Las enzimas son caras e inestables, lo que motiva la búsqueda de alternativas mejores. Los coensamblajes de metabolitos y metales, que imitan el funcionamiento de las metaloenzimas, tienen una alta eficiencia y gran estabilidad, incluso en condiciones extremas. Sin embargo, el estudio del vasto espacio químico de las enzimas naturales apenas ha comenzado. En el proyecto Meta2Zyme, financiado por el Consejo Europeo de Investigación, se examinará una matriz combinatoria de metabolitos e iones metálicos que se coensamblan en sitios activos catalíticos supramoleculares únicos, similares a la organización de las enzimas convencionales. El equipo del proyecto utilizará técnicas experimentales y computacionales avanzadas, incluidos modelos predictivos basados en inteligencia artificial, para identificar, optimizar y probar nuevas nanozimas en diversas aplicaciones. Gracias a la caracterización de estas nanoenzimas eficientes, en el proyecto se busca comprender mejor la evolución de las enzimas naturales y el diseño de nanomateriales catalíticos.

Objetivo

While enzymes are highly useful in various applications, their limited operational stability and production costs have led to an extensive search for stable catalytic agents that will retain the efficiency, specificity, and environmental-friendliness of natural enzymes. Despite extensive efforts, there is still an unmet need for improved enzyme mimics and novel concepts to discover and optimize such agents. Inspired by the catalytic activity of amyloids and the formation of amyloid-like assemblies by metabolites, our group pioneered the development of metabolite-metal co-assemblies that mimic the catalytic function of common metalloenzymes with remarkably safe and simple building blocks. Intriguingly, the assemblies exhibit high efficiency and exceptional robustness, even under extreme conditions of temperature, pH, and salinity that are impractical for enzymes. Yet, we had only explored a minute fraction of the chemical space as present in natural enzymes. In this project, we propose the first-ever systematic exploration of a vast combinatorial matrix consisting of metabolites and metal ions that co-assemble into unique supramolecular catalytic active sites, analogous to the organization of covalently bound residues and metal ions in conventional enzymes. The proposed work will involve advanced experimental and computational techniques, including artificial intelligence-driven predictive modelling based on functional, structural, and mechanistic data, to identify, optimize, and test the new nanozymes in various relevant application scenarios. Through this comprehensive study, we will not only identify and characterize highly efficient nanozymes, but also gain fundamental insights into the evolution of natural enzymes and design principles of catalytic nanomaterials. This high-risk/high-gain project has the potential to revolutionize the mimicking of enzymatic catalysis and develop robust, highly efficient, cost-effective, and eco-friendly catalytic assemblies.