ZEBRAFISH’S URICASE OXIDASE PRODUCTION OPTIMIZATION

The use of enzymes as biopharmaceuticals for the treatment of refractory gout and tumor lysis syndrome–associated hyperuricemia is a well-established approach in modern medicine. Among these, the most widely used enzymes are rasburicase and pegloticase; however, rasburicase has high immunogenicity that limits its application in long-term treatments, while pegloticase is further constrained by its high cost and restricted availability. . In addition, few studies have investigated alternative enzymes for this purpose. Among the potential alternatives, Zebrafish (Danio rerio) uricase oxidase stands out as a promising candidate. Zebrafish are evolutionarily closer to hominids than Aspergillus flavus and are widely recognized as a model organism, making further experimental studies both possible and relevant. Despite its potential, the optimal conditions for Zebrafish uricase oxidase biotechnological use have been poorly studied. The aim of this work was to optimize enzyme production parameters to increase the yield and develop a more efficient method. In this work, we successfully optimized the production of Zebrafish uricase, achieving higher yields in significantly shorter induction times compared to conventional protocols, without compromising protein concentration. The enzyme was obtained in a soluble form, with improved stability under specific buffer conditions. We are developing modified versions of the enzyme and comparing them with available commercial alternatives to enhance catalytic activity and therapeutic potential. These findings highlight Zebrafish uricase as a feasible alternative to currently used enzymes and provide a foundation for its future development as a biopharmaceutical for the treatment of hyperuricemic diseases.

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and by the Military Institute of Engineering (IME).