Advancing Cu/Zn Superoxide Dismutase (SOD1) production in Pichia pastoris: challenges, strategies, current research status, and future directions.

Cu/Zn Superoxide Dismutase (SOD1) plays a critical role in alleviating oxidative stress by catalyzing the conversion of superoxide radicals into oxygen and hydrogen peroxide. This review presents an in-depth analysis of the challenges and strategies involved in optimizing SOD1 production, with a focus on Pichia pastoris as an expression system. Key approaches such as the strategic selection of expression vectors, codon optimization, and the fine-tuning of fermentation parameters to maximize SOD1 yield are thoroughly explored. Advances in protein engineering, the co-expression of molecular chaperones, and the use of stabilizers and additives are also examined for their role in improving SOD1 stability and functionality. The review highlights the significant biomedical and industrial applications of overexpressed and thermostable SOD1, uncovering novel opportunities for therapeutic interventions and biotechnological innovations. Additionally, emerging technologies such as omics-based approaches, advanced protein engineering tools, and alternative host systems are discussed, offering new avenues for future research. This comprehensive review underscores the transformative potential of SOD1 optimization, positioning it at the forefront of scientific and technological advancements.