肝素是一种高度硫酸化的糖胺聚糖，被认为是一种不可缺少的抗凝剂，具有多种治疗应用，近一个世纪以来一直是医疗实践的中流砥柱。它的潜力超出了抗凝作用，在治疗炎症、癌症和 COVID-19 等传染病方面显示出前景。然而，目前其从动物组织中的来源由于结构可变和掺假而带来了挑战，影响了治疗效果和安全性。代谢工程和合成生物学的最新进展通过生物工程肝素生产提供了替代方案，尽管存在控制分子量和磺化模式等挑战。这篇综述提供了对最新进展的全面见解，包括：（i）原核系统中用于肝素生产的代谢工程策略； (ii) 生物工程肝素开发取得的进展； (iii) 推动真核系统产量提高的突破性方法。此外，它还探讨了重组中国仓鼠卵巢细胞在肝素合成中的潜力，讨论了最新进展、挑战和未来前景，从而开辟了生物医学研究的新途径。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Heparin, a highly sulfated glycosaminoglycan, is considered an indispensable anticoagulant with diverse therapeutic applications and has been a mainstay in medical practice for nearly a century. Its potential extends beyond anticoagulation, showing promise in treating inflammation, cancer, and infectious diseases such as COVID-19. However, its current sourcing from animal tissues poses challenges due to variable structures and adulterations, impacting treatment efficacy and safety. Recent advancements in metabolic engineering and synthetic biology offer alternatives through bioengineered heparin production, albeit with challenges such as controlling molecular weight and sulfonation patterns. This review offers comprehensive insight into recent advancements, encompassing: (i) the metabolic engineering strategies in prokaryotic systems for heparin production; (ii) strides made in the development of bioengineered heparin; and (iii) groundbreaking approaches driving production enhancements in eukaryotic systems. Additionally, it explores the potential of recombinant Chinese hamster ovary cells in heparin synthesis, discussing recent progress, challenges, and future prospects, thereby opening up new avenues in biomedical research.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.