Advances in the biosynthesis of heparosan, a key precursor of heparin

Heparin, a vital anticoagulant widely used in clinical practice, has traditionally been sourced through extraction from animal tissues. However, this production method faces significant challenges, including limited source availability, batch-to-batch variability, and potential safety risks associated with animal-derived products. These inherent limitations have prompted an urgent need for developing more efficient and consistent heparin production strategies. Recent advances in biotechnology have identified heparosan, a bacterial capsular polysaccharide, as a promising precursor for heparin production through targeted sulfation modifications. The application of metabolic engineering techniques has significantly enhanced the microbial synthesis of heparosan, paving the way for an innovative and environmentally friendly approach to heparin production. This emerging biotechnological method offers substantial advantages, including reduced production costs, increased yield consistency, and decreased dependence on animal-derived resources, while simultaneously addressing safety concerns associated with traditional methods. This comprehensive review systematically examines recent advancements in microbial heparosan synthesis, evaluates current challenges, and explores future directions in this rapidly evolving field.