Progress on the synthesis of bioengineered heparin as an alternative to animal-derived heparin active pharmaceutical ingredient.

Heparin, a clinically essential anticoagulant, has long been derived from animal sources, posing risks of contamination and supply chain instability. Bioengineered heparin, synthesized via microbial fermentation and enzymatic modification, offers a promising alternative with enhanced safety, homogeneity, and scalability. This review highlights recent advances in heparosan biosynthesis, enzymatic sulfation strategies, and analytical characterization for bioengineered heparin. Critical challenges remain, including precise control of heparosan molecular weight, optimization of sulfation patterns, demonstration of structural and functional equivalence to animal-derived heparin, and industrial-scale process validation. By combining synthetic biology with advanced bioprocessing and quality control, structure-defined bioengineered heparin is poised to become a sustainable, high-performance replacement for traditional heparin active pharmaceutical ingredient (API).