“Resurrected” human-source urate oxidase with high uricolytic activity and stability

As evidences showed that UOX(Gene ID: 391051), a single pseudogene formed after multiple mutations during human evolution, could be transcribed to mature mRNA and translated to two short peptides, we hypothesized that urate oxidase with higher homology with deduced human urate oxidase (dHU) might have lower immunogenicity. In this work, we constructed a "resurrected" human-source urate oxidase (rHU19) based on dHU. It obtained better uricolytic activity (8.29 U/mg) and catalytic efficiency (3.32 s−1 μM−1) compared with wild porcine urate oxidase (wPU) and FDA-approved porcine–baboon chimera (PBC). Maintaining high homology with dHU (93.75 %), rHU19 could be more suitable for the treatment of gout and hyperuricemia theoretically.