Controllable polysaccharide depolymerization by heparinases for efficient low molecular weight heparin production
2026
Fengling Yang | Ruirui Xu | Hao Huang | Jie Lu | Jiamin Feng | Xiaoyuan Sun | Jianghua Li | Guocheng Du | Zhen Kang
Low molecular weight heparins (LMWHs) are widely used in clinical anticoagulant therapy. Although most commercial LMWHs are still produced through chemical depolymerization, enzymatic depolymerization using heparinases has emerged as a highly attractive alternative due to its environmental friendliness, high selectivity, and superior preservation of native heparin bioactivity. Heparinases selectively cleave specific glycosidic bonds in unfractionated heparin (UFH), enabling precise and controllable depolymerization of polysaccharide chains and thereby generating LMWHs with well-defined structures and favorable anticoagulant properties, typically reflected by anti-Xa/anti-IIa activity ratios. Distinct classes of heparinases differ in substrate specificity and catalytic mechanisms, allowing targeted cleavage guided by sulfation patterns and structural features. This review summarizes the substrate preferences, crystal structures, and catalytic mechanisms of heparinases, highlighting their mechanistic basis for controlled polysaccharide depolymerization. Recent advances in protein engineering and LMWHs production strategies are discussed, along with emerging trends and future directions aimed at enhancing catalytic performance and enabling more tailored, efficient, and sustainable LMWHs manufacturing.
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