Synthetic biology for heparin biomanufacturing

Heparin, mainly used as an anticoagulant, has also shown potential in the treatment of diseases such as inflammation and cancer. Currently, heparin is mainly extracted from the intestinal mucosa of pigs. However, due to concerns about disease transmission and contamination associated with animal-derived products, biomanufacturing techniques have been explored as alternative production methods. Through enzyme engineering, metabolic engineering, and synthetic biology approaches, the heparin biosynthetic pathways have been systematically optimized. The main biomanufacturing techniques include in vivo/in vitro combination strategy (microbial heparosan fermentation followed by chemoenzymatic modification) and de novo biosynthesis. This article comprehensively discusses the latest advancements, challenges, and future perspectives of these heparin biomanufacturing techniques.