Research advances in biosynthesis of chondroitin sulfate and its oligosaccharides

ZHANG Jin; ZHANG Weijiao; XIONG Haibo; XIE Zhuan; XU Ruirui; KANG Zhen

doi:10.12211/2096-8280.2025-051

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Research advances in biosynthesis of chondroitin sulfate and its oligosaccharides

Invited Review | 更新时间：2026-09-04

- Research advances in biosynthesis of chondroitin sulfate and its oligosaccharides
- 硫酸软骨素及其寡聚糖的生物合成进展
- Synthetic Biology Journal Vol. 7, Issue 4, Pages: 870-887(2026)
- 作者机构：
  
  1.江南大学生物工程学院，糖化学与生物技术教育部重点实验室，江苏无锡 214122
  2.江南大学未来食品科学中心，江苏无锡 214122
  3.江南大学生物工程学院，工业生物技术教育部重点实验室，江苏无锡 214122
  4.江南大学，江苏省合成生物基础研究中心，江苏无锡 214122
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-051
  CLC： Q815
- Received：29 May 2025，
  
  Revised：2025-08-13，
  
  Published：31 August 2026
- 稿件说明：
移动端阅览
张瑾，张维娇，熊海波，谢专，胥睿睿，康振. 硫酸软骨素及其寡聚糖的生物合成进展［J］. 合成生物学， 2026， 7（4）： 870-887

ZHANG Jin， ZHANG Weijiao， XIONG Haibo， XIE Zhuan， XU Ruirui， KANG Zhen. Research advances in biosynthesis of chondroitin sulfate and its oligosaccharides［J］. Synthetic Biology Journal， 2026， 7（4）： 870-887
张瑾，张维娇，熊海波，谢专，胥睿睿，康振. 硫酸软骨素及其寡聚糖的生物合成进展［J］. 合成生物学， 2026， 7（4）： 870-887 DOI： 10.12211/2096-8280.2025-051.

ZHANG Jin， ZHANG Weijiao， XIONG Haibo， XIE Zhuan， XU Ruirui， KANG Zhen. Research advances in biosynthesis of chondroitin sulfate and its oligosaccharides［J］. Synthetic Biology Journal， 2026， 7（4）： 870-887 DOI： 10.12211/2096-8280.2025-051.

摘要

硫酸软骨素（chondroitin sulfate，CS）是一类广泛存在于动物结缔组织中的糖胺聚糖，具有良好的抗炎、保水、抗氧化等多种生物活性，广泛应用于关节保健品、化妆品及医药等领域。然而，传统的动物组织提取工艺面临分子量不均一、潜在病原体风险、工艺周期长、环境污染等问题，难以满足高标准应用领域对产品纯度与安全性的要求。随着合成生物学的发展，利用工程化微生物实现CS的绿色制造已经成为研究热点。通过在微生物细胞工厂中重构CS前体合成路径和构建高效硫酸化修饰体系，已初步实现CS的可控生物合成，并通过引入CS降解酶实现了CS寡聚糖的制备。本综述系统梳理了CS的生物合成研究进展，重点讨论了前体软骨素合成途径优化及关键酶元件设计优化、CS的生物合成体系构建与优化及寡聚糖的精准制备技术。基于这些最新的研究进展，本文深入分析了CS及其寡聚糖生物合成面临的主要挑战，包括前体供应不足、硫酸基转移酶催化活性及稳定性差、软骨素糖链聚合与硫酸化修饰的时空协同调控不明确，以及CS寡聚糖制备中水解酶催化效率低下等问题，并对CS及其寡聚糖生物合成研究的未来发展方向进行了展望：未来研究应着力通过动态代谢调控、人工智能辅助酶改造以及合成生物学与酶工程的深度融合，实现CS绿色、高效的规模化生产及推进其在多领域的创新应用。

Abstract

Chondroitin sulfate (CS) is a glycosaminoglycan abundantly present throughout animal connective tissues

renowned for its spectrum of biological activities such as anti-inflammatory action

profound moisturizing capacity

and potent antioxidant effects.Owing to these beneficial properties

CS has been extensively utilized in joint health supplements

cosmetics

and pharmaceuticals. Traditionally

CS is extracted from animal tissues. However

this conventional extraction process presents several significant challenges

including heterogeneity in molecular weight

potential risks of pathogen contamination

long production cycles

and environmental pollution caused by chemical reagents and waste disposal. Such issues limit the ability of animal-derived CS to meet the stringent purity

safety

and quality standards required in high-end applications

especially in precision medicine and advanced biomaterials. With the rapid advancement of synthetic biology

the green and sustainable production of CS using engineered microbial cell factories has emerged as a key area of research. By reconstructing the CS precursor synthesis pathway and constructing an efficient sulfation modification system in microbial cell factories

the controlled biological synthesis of CS has been initially achieved

and the preparation of CS oligosaccharides has been realized by introducing CS degrading enzymes. This microbial synthesis approach not only addresses safety and environmental concerns but also offers advantages in scalability

product consistency

and cost-effectiveness.This review article provides a comprehensive summary of recent progress in biosynthesis of CS. It focuses on analyzing the optimization strategies for the synthesis pathways of chondroitin precursors and the design and engineering of key enzyme components. It delves deeply into the construction of the CS biosynthetic system and the multi-level optimization approaches. Meanwhile

the paper also provides a detailed introduction to the precise preparation processes of CS oligosaccharides

laying a solid foundation for achieving biosynthesized CS with highly consistent structural and functional properties. Based on these latest research advancements

this paper thoroughly analyzes the main challenges faced in the biosynthesis of CS and its oligosaccharides

including inadequate supply of precursors

insufficient catalytic activity and instability of sulfotransferase

unclear spatiotemporal coordination regulation of chondroitin sulfate glycan chain polymerization and sulfation modification

as well as low catalytic efficiency of hydrolysis enzymes in oligosaccharide preparation. It also provides a perspective on the future development direction of CS biosynthesis research: future studies should focus on achieving green and efficient large-scale production of CS and promoting its innovative applications in multiple fields through dynamic metabolic regulation

artificial intelligence-assisted enzyme modification

and the deep integration of synthetic biology and enzyme engineering.

关键词

Keywords

references

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