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.
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