%0 Journal Article
%T Designing Therapeutic Enzymes across Competing Biological Constraints: A Conceptual Framework Integrating Catalytic Performance, Glycosylation, Tissue Uptake, and Immune Recognition in Protein Engineering
%A Yuki Sasaki
%A Mei Lin
%A Haruto Ito
%J Journal of Biochemical Technology
%@ 0974-2328
%D 2026
%V 17
%N 4
%R 10.51847/yy3W8KxMD0
%P 49-57
%X Therapeutic enzymes are often engineered through molecular objectives that can be measured efficiently in vitro, including catalytic activity, substrate selectivity, folding stability, and expression yield. Yet therapeutic performance emerges only after these molecular properties interact with glycosylation, systemic persistence, receptor-mediated distribution, tissue access, intracellular trafficking, and host immune recognition. Optimizing a single measurable attribute can therefore improve one component of performance while leaving another unchanged or even impaired. This article develops a non-empirical conceptual account of therapeutic-enzyme design as a multicriteria biological problem in which intrinsic catalytic competence is necessary but insufficient for therapeutic quality. The analysis distinguishes five linked but non-equivalent levels: catalytic and conformational performance; glycosylation-dependent stability and distribution; tissue and cellular uptake; intracellular functional availability; and immune compatibility during repeated exposure. Evidence from enzyme engineering, glycoprotein design, lysosomal-enzyme trafficking, protein delivery, and enzyme-replacement therapy is used to identify where these dimensions reinforce or constrain one another. Particular attention is given to situations in which assay-defined improvements fail to predict physiological performance because of receptor biology, organ-specific uptake, intracellular localization, or immunogenicity. The resulting account does not prescribe a universal optimal enzyme architecture. Instead, it frames therapeutic engineering as the identification of context-dependent combinations of molecular and biological properties whose adequacy must be judged at the scale at which the therapy is intended to function. This perspective provides a basis for evaluating therapeutic-enzyme candidates without reducing their quality to catalytic performance alone.

 
%U https://jbiochemtech.com/article/designing-therapeutic-enzymes-across-competing-biological-constraints-a-conceptual-framework-integr-xdkeoat7joxoaxk