Creation of Artificial Subcellular Organelles Using Compartmentalized Escherichia coli Bodies for Artificial Metalloenzyme-Mediated Abiotic Catalysis in Eukaryotic Cells

• DOI: 10.1021/jacs.5c00473
• Publication Date: 2025-04-24T07:15:04Z
• Authors: Tong Wu; Yating Fei; Yingjiao Deng; Xianhui Chen; Yuli Duan; Ying Liu; Yugang Bai
• Keywords: Organelle

Artificial metalloenzymes (ArMs) stand out as excellent tools mediating intracellular abiotic transformations due to their multifaceted advantages, including adaptability through directed evolution and availability whole-cell catalysts. However, the applications of ArMs exogenous agents in eukaryotic systems remain challenging issues with protein purification delivery, metalloenzyme stability, complex catalyst preparation. In this article, we present a method inspired by nature's endosymbiotic process, enabling direct use residing within bacterial cells that express them whole-cell-based catalytic platforms cells. This approach utilizes HaloTag-SNAPTag fusion ArM scaffold, which undergoes liquid-liquid phase separation form sanctuaries Escherichia coli for different created from same protein. Such compartmentalized E. are then sterilized granted cell permeability polymer decoration so they may enter work artificial subcellular organelles, using those well-protected within. We further demonstrate potential strategy therapeutic proof-of-concept demonstrations, showing these encapsulated can be viable options pathogen elimination cancer therapy prodrug activation live animals. Likely, will suggest pathway expanding chemical biology biomedicine.