A Dual‐Metal‐Catalyzed Sequential Cascade Reaction in an Engineered Protein Cage**

Abstract

AbstractHerein, 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.