A Dual‐Metal‐Catalyzed Sequential Cascade Reaction in an Engineered Protein Cage**
Paul Ebensperger, Mariia Zmyslia, Philipp Lohner, Judith Braunreuther, Benedikt Deuringer, Anita Becherer, Regine Süss, Anna Fischer, Claudia Jessen‐Trefzer
Abstract
Herein, we describe the creation of an artificial protein cage housing a dual-metal-tagged guest protein that catalyzes a linear, two-step sequential cascade reaction. The guest protein consists of a fusion protein of HaloTag and monomeric rhizavidin. Inside the protein capsid, we established a ruthenium-catalyzed allylcarbamate deprotection reaction followed by a gold-catalyzed ring-closing hydroamination reaction that led to indoles and phenanthridines with an overall yield of up to 66 % in aqueous solutions. Furthermore, we show that the encapsulation stabilizes the metal catalysts against deactivation by air, proteins and cell lysate.