Cyanobacteria‐Inspired Temperature‐Sensitive Dormant Multi‐Enzyme Factory for Sustainable Urea Ammonia Detoxification and Amino Acid Bioconversion

ABSTRACT Ammonia and urea are typical nitrogen‐containing waste products that are highly toxic to patients with kidney disease. Thus, substantial dialysate volumes are needed for effective clearance. Wearable artificial kidneys aim to achieve dialysate regeneration; however, their development is hindered by the challenges of expensive cofactor recycling and poor biocatalyst stability. Inspired by cyanobacteria, this study constructed a biomimetic multi‐enzyme factory for urea ammonia sustainable bioconversion. Polyether sulfone and gelatin/polyethyleneimine were used to construct a biomimetic cyanobacterial cell factory with immobilized enzymes and a cofactor to achieve the efficient and sustainable bioconversion of urea‐ammonia to glutamic acid in a continuous peritoneal dialysis flow reactor. Approximately 80% of the urea clearance capacity was retained after 10 cycles of peritoneal dialysate regeneration in vitro. In addition, reversible cross‐linking of the gelatin triple‐helix structure endowed the biomimetic cells with unique temperature‐sensitivity. More than 90% of the hydrated enzymatic activity was retained after storage at 4°C and approximately 65% after nearly one month at room temperature. When the gelatin network underwent uncoiling at 37°C, it could be activated within 40 s. The study findings provide a sustainable strategy for urea‐ammonia detoxification and valorization, dialysate regeneration, and a universal biomimetic catalysis platform.