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

Xiaohan Jiang¹, Bo Zhang², Xue Cai¹, Zhiqiang Liu³, Yuguo Zheng¹

Affiliations

¹ Zhejiang Key Laboratory of Bioorganic Synthesis, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; Huadong Industrial Technology Institute of Synthetic Biology, Hangzhou, Zhejiang 310014, China; State Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.
² Zhejiang Key Laboratory of Bioorganic Synthesis, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; State Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.
³ Zhejiang Key Laboratory of Bioorganic Synthesis, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; Huadong Industrial Technology Institute of Synthetic Biology, Hangzhou, Zhejiang 310014, China; State Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China. Electronic address: microliu@zjut.edu.cn.

PMID: 40912801
DOI: 10.1016/j.carbpol.2025.124099

Review

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

Xiaohan Jiang et al. Carbohydr Polym. 2025.

. 2025 Nov 15;368(Pt 1):124099.

doi: 10.1016/j.carbpol.2025.124099. Epub 2025 Jul 24.

Authors

Xiaohan Jiang¹, Bo Zhang², Xue Cai¹, Zhiqiang Liu³, Yuguo Zheng¹

Affiliations

¹ Zhejiang Key Laboratory of Bioorganic Synthesis, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; Huadong Industrial Technology Institute of Synthetic Biology, Hangzhou, Zhejiang 310014, China; State Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.
² Zhejiang Key Laboratory of Bioorganic Synthesis, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; State Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.
³ Zhejiang Key Laboratory of Bioorganic Synthesis, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; Huadong Industrial Technology Institute of Synthetic Biology, Hangzhou, Zhejiang 310014, China; State Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China. Electronic address: microliu@zjut.edu.cn.

PMID: 40912801
DOI: 10.1016/j.carbpol.2025.124099

Abstract

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).

Keywords: Bioengineered heparin; Heparosan; Microbial-enzymatic synthesis; Molecular weight control; Quality control; Sulfation modification.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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

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

Authors

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Abstract

Conflict of interest statement

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