硫酸软骨素及其寡聚糖的生物合成进展

张瑾; 张维娇; 熊海波; 谢专; 胥睿睿; 康振

doi:10.12211/2096-8280.2025-051

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硫酸软骨素及其寡聚糖的生物合成进展

特约评述 | 更新时间：2026-09-04

- 硫酸软骨素及其寡聚糖的生物合成进展
- Research advances in biosynthesis of chondroitin sulfate and its oligosaccharides
- 合成生物学 2026年7卷第4期页码：870-887
- 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：
  
  张瑾（2002—），女，硕士研究生。研究方向为硫酸软骨素的生物合成与酶工程改造应用。E-mail：6240201068@stu.jiangnan.edu.cn
  康振（1982—），男，博士，教授，博士生导师。研究方向为微生物合成生物学与生物制造研究。E-mail：zkang@jiangnan.edu.cn
- 基金信息：
  
  国家重点研发计划项目(2024YFF1106300);国家自然科学基金项目(32400056);江苏省合成生物基础研究中心资助(BK20233003);江苏省基础研究计划自然科学基金-青年基金项目(BK20241616);国家资助博士后研究人员计划项目(GZC20240607);中央高校基本科研基金(JUSRP622003)
- DOI：10.12211/2096-8280.2025-051
  中图分类号： Q815
- 收稿：2025-05-29，
  
  修回：2025-08-13，
  
  纸质出版：2026-08-31
- 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

张茜 , 王畅 , 梁琛 , 等 . 硫酸软骨素应用于骨修复材料中的研究进展 [J ] . 口腔医学 , 2023 , 43 ( 1 ): 88 - 91 .

ZHANG Q , WANG C , LIANG C , et al . Progress of research on application of chondroitin sulfate in osteogenic repair materials [J ] . Stomatology , 2023 , 43 ( 1 ): 88 - 91 .

ANDREWS S , CHENG A , STEVENS H , et al . Chondroitin sulfate glycosaminoglycan scaffolds for cell and recombinant protein-based bone regeneration [J ] . STEM CELLS Translational Medicine , 2019 , 8 ( 6 ): 575 - 585 .

SIRKO S , VON HOLST A , WIZENMANN A , et al . Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells [J ] . Development , 2007 , 134 ( 15 ): 2727 - 2738 .

蓝伟 , 陈建平 . 硫酸软骨素的生物活性及其构效关系研究进展 [J ] . 食品安全质量检测学报 , 2022 , 13 ( 15 ): 4924 - 4932 .

LAN W , CHEN J P . Research progress on biological activity and structure-activity relationship of chondroitin sulfate [J ] . Journal of Food Safety & Quality , 2022 , 13 ( 15 ): 4924 - 4932 .

BISHNOI M , JAIN A , HURKAT P , et al . Chondroitin sulphate: a focus on osteoarthritis [J ] . Glycoconjugate Journal , 2016 , 33 ( 5 ): 693 - 705 .

田雪 , 彭旭东 , 尹娇 , 等 . 硫酸软骨素及衍生物在医药领域中的研究进展 [J ] . 临床医学进展 , 2020 , 10 ( 12 ): 2960 - 2973 .

TIAN X , PENG X D , YIN J , et al . Advanced research of chondroitin sulfate and its derivatives in the medicine field [J ] . Advances in Clinical Medicine , 2020 , 10 ( 12 ): 2960 - 2973 .

付常芳 , 周伟 , 高奇 , 等 . 硫酸软骨素及其衍生物研究进展 [J ] . 医药导报 , 2023 , 42 ( 5 ): 688 - 691 .

FU C F , ZHOU W , GAO Q , et al . Research progress of chondroitin sulfate and its derivatives [J ] . Herald of Medicine , 2023 , 42 ( 5 ): 688 - 691 .

SAHA S K , ZHU Y , MURRAY P , et al . Future proofing of chondroitin sulphate production: importance of sustainability and quality for the end-applications [J ] . International Journal of Biological Macromolecules , 2024 , 267 : 131577 .

LI J E , ZHANG J H , TAN H R . Microbial production of chondroitin sulfate and its derivatives [J ] . Science China Life Sciences , 2025 , 68 ( 3 ): 871 - 873 .

VOLPI N . Chondroitin sulfate safety and quality [J ] . Molecules , 2019 , 24 ( 8 ): 1447 .

STELLAVATO A , RESTAINO O F , VASSALLO V , et al . Comparative analyses of pharmaceuticals or food supplements containing chondroitin sulfate: are their bioactivities equivalent? [J ] . Advances in Therapy , 2019 , 36 ( 11 ): 3221 - 3237 .

邹德生 . 硫酸软骨素的生产工艺研究进展 [J ] . 现代食品 , 2018 ( 22 ): 22 - 24 .

ZOU D S . Process on preparation technology of chondroitin sulfate [J ] . Modern Food , 2018 ( 22 ): 22 - 24 .

WANG W S , SHI L R , QIN Y , et al . Research and application of chondroitin sulfate/dermatan sulfate-degrading enzymes [J ] . Frontiers in Cell and Developmental Biology , 2020 , 8 : 560442 .

WANG K Y , QI L W , ZHAO L Y , et al . Degradation of chondroitin sulfate: mechanism of degradation, influence factors, structure-bioactivity relationship and application [J ] . Carbohydrate Polymers , 2023 , 301 : 120361 .

VALCARCEL J , NOVOA-CARBALLAL R , PÉREZ-MARTÍN R I , et al . Glycosaminoglycans from marine sources as therapeutic agents [J ] . Biotechnology Advances , 2017 , 35 ( 6 ): 711 - 725 .

CRESS B F , GREENE Z R , LINHARDT R J , et al . Draft genome sequence of Escherichia coli strain ATCC 23502 (serovar O5:K4:H4) [J ] . Genome Announcements , 2013 , 1 ( 2 ): e00046-13 .

SHEN Q S , GUO Y J , WANG K Y , et al . A review of chondroitin sulfate’s preparation, properties, functions, and applications [J ] . Molecules , 2023 , 28 ( 20 ): 7093 .

ZHOU C , MI S , LI J , et al . Purification, characterisation and antioxidant activities of chondroitin sulphate extracted from Raja porosa cartilage [J ] . Carbohydrate Polymers , 2020 , 241 : 116306 .

TAT S K , PELLETIER J P , MINEAU F , et al . Variable effects of 3 different chondroitin sulfate compounds on human osteoarthritic cartilage/chondrocytes: relevance of purity and production process [J ] . The Journal of Rheumatology , 2010 , 37 ( 3 ): 656 - 664 .

CIMINI D , RESTAINO O F , SCHIRALDI C . Microbial production and metabolic engineering of chondroitin and chondroitin sulfate [J ] . Emerging Topics in Life Sciences , 2018 , 2 ( 3 ): 349 - 361 .

YANG F , LI Y G , WANG L , et al . Full-thickness osteochondral defect repair using a biodegradable bilayered scaffold of porous zinc and chondroitin sulfate hydrogel [J ] . Bioactive Materials , 2024 , 32 : 400 - 414 .

田伟功 , 王琳琳 , 杜茜茜 , 等 . 低分子量硫酸软骨素体外酵解特征及其对肠道菌群的调节作用 [J ] . 现代食品科技 , 2023 , 39 ( 10 ): 59 - 68 .

TIAN W G , WANG L L , DU Q Q , et al . In vitro fermentation characteristics of low-molecular-weight chondroitin sulfate and its regulatory effects on gut microbiota [J ] . Modern Food Science and Technology , 2023 , 39 ( 10 ): 59 - 68 .

MIN D , PARK S , KIM H , et al . Potential anti-ageing effect of chondroitin sulphate through skin regeneration [J ] . International Journal of Cosmetic Science , 2020 , 42 ( 5 ): 520 - 527 .

袁媛 , 宋兵兵 , 陈菁 , 等 . 不同来源硫酸软骨素的结构特征及抗氧化活性与降脂活性比较 [J ] . 食品工业科技 , 2026 , 47 ( 3 ): 42 - 51 .

YUAN Y , SONG B B , CHEN J , et al . Comparative analysis of structural characterization, antioxidant, and hypolipidemic activities of chondroitin sulfate from different sources [J ] . Science and Technology of Food Industry , 2026 , 47 ( 3 ): 42 - 51 .

SHIDA M , MIKAMI T , TAMURA J I , et al . Chondroitin sulfate-D promotes neurite outgrowth by acting as an extracellular ligand for neuronal integrin αVβ3 [J ] . Biochimica et Biophysica Acta (BBA) - General Subjects , 2019 , 1863 ( 9 ): 1319 - 1331 .

SWARUP V P , HSIAO T W , ZHANG J X , et al . Exploiting differential surface display of chondroitin sulfate variants for directing neuronal outgrowth [J ] . Journal of the American Chemical Society , 2013 , 135 ( 36 ): 13488 - 13494 .

FAHEEM S , HAMEED H , PAIVA-SANTOS A C , et al . The role of chondroitin sulphate as a potential biomaterial for hepatic tissue regeneration: a comprehensive review [J ] . International Journal of Biological Macromolecules , 2024 , 280 : 136332 .

PENG C E , WANG Q B , JIAO R M , et al . A novel chondroitin sulfate E from Dosidicus gigas cartilage and its antitumor metastatic activity [J ] . Carbohydrate Polymers , 2021 , 262 : 117971 .

KASTANA P , CHOLEVA E , POIMENIDI E , et al . Insight into the role of chondroitin sulfate E in angiogenesis [J ] . The FEBS Journal , 2019 , 286 ( 15 ): 2921 - 2936 .

DEANGELIS P L , PADGETT-MCCUE A J . Identification and molecular cloning of a chondroitin synthase from Pasteurella multocida type F [J ] . Journal of Biological Chemistry , 2000 , 275 ( 31 ): 24124 - 24129 .

COUTO M R , RODRIGUES J L , RODRIGUES L R . Heterologous production of chondroitin [J ] . Biotechnology Reports , 2022 , 33 : e00710 .

RODRIGUEZ M L , JANN B , JANN K . Structure and serological characteristics of the capsular K4 antigen of Escherichia coli O5:K4:H4, a fructose-containing polysaccharide with a chondroitin backbone [J ] . European Journal of Biochemistry , 1988 , 177 ( 1 ): 117 - 124 .

LIU J , YANG A H , LIU J , et al . KfoE encodes a fructosyltransferase involved in capsular polysaccharide biosynthesis in Escherichia coli K4 [J ] . Biotechnology Letters , 2014 , 36 ( 7 ): 1469 - 1477 .

CIMINI D , CARLINO E , GIOVANE A , et al . Engineering a branch of the UDP-precursor biosynthesis pathway enhances the production of capsular polysaccharide in Escherichia coli O5:K4:H4 [J ] . Biotechnology Journal , 2015 , 10 ( 8 ): 1307 - 1315 .

VENTURA C L , CARTEE R T , FORSEE W T , et al . Control of capsular polysaccharide chain length by UDP-sugar substrate concentrations in Streptococcus pneumoniae [J ] . Molecular Microbiology , 2006 , 61 ( 3 ): 723 - 733 .

GOMES A M V , NETTO J H C M , CARVALHO L S , et al . Heterologous hyaluronic acid production in Kluyveromyces lactis [J ] . Microorganisms , 2019 , 7 ( 9 ): 294 .

CIMINI D , RUSSO R , D’AMBROSIO S , et al . Physiological characterization and quantitative proteomic analyses of metabolically engineered E . coli K4 strains with improved pathways for capsular polysaccharide biosynthesis [J ] . Biotechnology and Bioengineering , 2018 , 115 ( 7 ): 1801 - 1814 .

JIN P , ZHANG L P , YUAN P H , et al . Efficient biosynthesis of polysaccharides chondroitin and heparosan by metabolically engineered Bacillus subtilis [J ] . Carbohydrate Polymers , 2016 , 140 : 424 - 432 .

D’AMBROSIO S , ALFANO A , CASSESE E , et al . Production and purification of higher molecular weight chondroitin by metabolically engineered Escherichia coli K4 strains [J ] . Scientific Reports , 2020 , 10 : 13200 .

张权 , 酉相成 , 陈修来 , 等 . 强化前体(UDP-GalNAc)合成路径提高果糖软骨素的生产 [J ] . 食品与生物技术学报 , 2020 , 39 ( 3 ): 71 - 80 .

ZHANG Q , YOU X C , CHEN X L , et al . Improving fructosylated chondroitin production by enhancement of UDP-GalNAc synthetic pathway [J ] . Journal of Food Science and Biotechnology , 2020 , 39 ( 3 ): 71 - 80 .

CHENG F Y , LUO-ZHONG S J , YU H M , et al . Biosynthesis of chondroitin in engineered Corynebacterium glutamicum [J ] . Journal of Microbiology and Biotechnology , 2019 , 29 ( 3 ): 392 - 400 .

CIMINI D , DE ROSA M , CARLINO E , et al . Homologous overexpression of rfaH in E . coli K4 improves the production of chondroitin-like capsular polysaccharide [J ] . Microbial Cell Factories , 2013 , 12 : 46 .

WU Q L , YANG A H , ZOU W , et al . Transcriptional engineering of Escherichia coli K4 for fructosylated chondroitin production [J ] . Biotechnology Progress , 2013 , 29 ( 5 ): 1140 - 1149 .

WU Y K , CHEN T C , LIU Y F , et al . CRISPRi allows optimal temporal control of N -acetylglucosamine bioproduction by a dynamic coordination of glucose and xylose metabolism in Bacillus subtilis [J ] . Metabolic Engineering , 2018 , 49 : 232 - 241 .

PEETERMANS A , FOULQUIÉ-MORENO M R , THEVELEIN J M . Mechanisms underlying lactic acid tolerance and its influence on lactic acid production in Saccharomyces cerevisiae [J ] . Microbial Cell , 2021 , 8 ( 6 ): 111 - 130 .

ZHANG Q , YAO R , CHEN X L , et al . Enhancing fructosylated chondroitin production in Escherichia coli K4 by balancing the UDP-precursors [J ] . Metabolic Engineering , 2018 , 47 : 314 - 322 .

ZHAO C L , LI X M , GUO L , et al . Reprogramming metabolic flux in Escherichia coli to enhance chondroitin production [J ] . Advanced Science , 2024 , 11 ( 10 ): 2307351 .

DEANGELIS P L , GUNAY N S , TOIDA T , et al . Identification of the capsular polysaccharides of type D and F Pasteurella multocida as unmodified heparin and chondroitin, respectively [J ] . Carbohydrate Research , 2002 , 337 ( 17 ): 1547 - 1552 .

WANG T T , ZHU C Y , ZHENG S , et al . Identification and characterization of a chondroitin synthase from Avibacterium paragallinarum [J ] . Applied Microbiology and Biotechnology , 2018 , 102 ( 11 ): 4785 - 4797 .

GREEN D E , DEANGELIS P L . Identification of a chondroitin synthase from an unexpected source, the green sulfur bacterium Chlorobium phaeobacteroides [J ] . Glycobiology , 2017 , 27 ( 5 ): 469 - 476 .

CIMINI D , FANTACCIONE S , VOLPE F , et al . IS2-mediated overexpression of kfoC in E . coli K4 increases chondroitin-like capsular polysaccharide production [J ] . Applied Microbiology and Biotechnology , 2014 , 98 ( 9 ): 3955 - 3964 .

ZANFARDINO A , RESTAINO O F , NOTOMISTA E , et al . Isolation of an Escherichia coli K4 kfoC mutant over-producing capsular chondroitin [J ] . Microbial Cell Factories , 2010 , 9 : 34 .

WANG Y Q , LI S , XU X , et al . Chemoenzymatic synthesis of homogeneous chondroitin polymers and its derivatives [J ] . Carbohydrate Polymers , 2020 , 232 : 115822 .

TITHI A D , SONG Y F , PASKALEVA E , et al . Biosynthesis of animal-free recombinant chondroitin sulfate E using a functional chondroitin sulfotransferase in E . coli [J ] . Applied Microbiology and Biotechnology , 2024 , 108 ( 1 ): 440 .

ZHOU Z X , LI Q , HUANG H , et al . A microbial-enzymatic strategy for producing chondroitin sulfate glycosaminoglycans [J ] . Biotechnology and Bioengineering , 2018 , 115 ( 6 ): 1561 - 1570 .

JIN X R , LI Q , WANG Y , et al . Optimizing the sulfation-modification system for scale preparation of chondroitin sulfate A [J ] . Carbohydrate Polymers , 2020 , 246 : 116570 .

盛靖雨 , 金学荣 , 胥睿睿 , 等 . 基于工程化毕赤酵母一锅法合成硫酸软骨素A [J ] . 生物工程学报 , 2022 , 38 ( 7 ): 2594 - 2605 .

SHENG J Y , JIN X R , XU R R , et al . One-pot synthesis of chondroitin sulfate A by engineered Pichia pastoris [J ] . Chinese Journal of Biotechnology , 2022 , 38 ( 7 ): 2594 - 2605 .

ZHANG W J , ZHANG P , WANG H , et al . Enha ncing the expression of chondroitin 4- O -sulfotransferase for one-pot enzymatic synthesis of chondroitin sulfate A [J ] . Carbohydrate Polymers , 2024 , 337 : 122158 .

LIU H Y , WEI W Q , PANG Z X , et al . Protein engineering, cofactor engineering, and surface display engineering to achieve whole-cell catalytic production of chondroitin sulfate A [J ] . Biotechnology and Bioengineering , 2023 , 120 ( 7 ): 1784 - 1796 .

WANG Z H , SONG W , WEI W Q , et al . Structural and mechanism-based engineering of sulfotransferase CHST15 for the efficient synthesis of chondroitin sulfate E [J ] . Applied and Environmental Microbiology , 2025 , 91 ( 1 ): e01573-24 .

BADRI A , WILLIAMS A , AWOFIRANYE A , et al . Complete biosynthesis of a sulfated chondroitin in Escherichia coli [J ] . Nature Communications , 2021 , 12 : 1389 .

JIN X R , ZHANG W J , WANG Y , et al . Biosynthesis of non-animal chondroitin sulfate from methanol using genetically engineered Pichia pastoris [J ] . Green Chemistry , 2021 , 23 ( 12 ): 4365 - 4374 .

GU S M , ZHANG F , LI Z Y , et al . Engineering a novel adenine-sulfotransferase for efficient synthesis of PAPS and chondroitin sulfate in microbial cells [J ] . Trends in Biotechnology , 2025 , 43 ( 10 ): 2609 - 2626 .

赵春雷 , 郭亮 , 高聪 , 等 . 代谢工程改造大肠杆菌生产软骨素 [J ] . 化工学报 , 2023 , 74 ( 5 ): 2111 - 2122 .

ZHAO C L , GUO L , GAO C , et al . Metabolic engineering of Escherichia coli for chondroitin production [J ] . CIESC Journal , 2023 , 74 ( 5 ): 2111 - 2122 .

XIONG H B , YANG X G , ZHANG W J , et al . Engineering Komagataella phaffii cell factories for the production of chondroitin sulfate A with high sulfation degree [J ] . Chemical Engineering Journal , 2025 , 520 : 165780 .

ZHANG W J , XU R R , CHEN J M , et al . Advances and challenges in biotechnological production of chondroitin sulfate and its oligosaccharides [J ] . International Journal of Biological Macromolecules , 2023 , 253 ( Pt 1 ): 126551 .

BURKART M D , IZUMI M , WONG C H . Enzymatic regeneration of 3′-phosphoadenosine-5′-phosphosulfate using aryl sulfotransferase for the preparative enzymatic synthesis of sulfated carbohydrates [J ] . Angewandte Chemie International Edition , 1999 , 38 ( 18 ): 2747 - 2750 .

ZHOU Z X , LI Q , XU R R , et al . Secretory expression of the rat aryl sulfotransferases Ⅳ with improved catalytic efficiency by molecular engineering [J ] . 3 Biotech , 2019 , 9 ( 6 ): 246 .

BURKART M D , IZUMI M , CHAPMAN E , et al . Regeneration of PAPS for the enzymatic synthesis of sulfated oligosaccharides [J ] . The Journal of Organic Chemistry , 2000 , 65 ( 18 ): 5565 - 5574 .

LIU K F , CHEN X L , ZHONG Y L , et al . Rational design of a highly efficient catalytic system for the production of PAPS from ATP and its application in the synthesis of chondroitin sulfate [J ] . Biotechnology and Bioengineering , 2021 , 118 ( 11 ): 4503 - 4515 .

XU R R , WANG Y , HUANG H , et al . Closed-loop system driven by ADP phosphorylation from pyrophosphate affords equimolar transformation of ATP to 3′-phosphoadenosine-5′- phosphosulfate [J ] . ACS Catalysis , 2021 , 11 ( 16 ): 10405 - 10415 .

XU R R , ZHANG W , XI X T , et al . Engineering sulfonate group donor regeneration systems to boost biosynthesis of sulfated compounds [J ] . Nature Communications , 2023 , 14 : 7297 .

KANG H G , EVERS M R , XIA G Q , et al . Molecular cloning and characterization of chondroitin-4- O -sulfotransferase-3. A novel member of the HNK-1 family of sulfotransferases [J ] . The Journal of Biological Chemistry , 2002 , 277 ( 38 ): 34766 - 34772 .

HE W Q , ZHU Y Y , SHIRKE A , et al . Expression of chondroitin-4- O -sulfotransferase in Escherichia coli and Pichia pastoris [J ] . Applied Microbiology and Biotechnology , 2017 , 101 ( 18 ): 6919 - 6928 .

YUSA A , KITAJIMA K , HABUCHI O . N-linked oligosaccharides are required to produce and stabilize the active form of chondroitin 4-sulphotransferase-1 [J ] . The Biochemical Journal , 2005 , 388 ( Pt 1 ): 115 - 121 .

谢专 , 张维娇 , 熊海波 , 等 . 毕赤酵母高效表达软骨素4- O -磺基转移酶 [J ] . 食品与发酵工业 , 2026 , 52 ( 1 ): 1 - 10 .

XIE Z , ZHANG W J , XIONG H B , et al . Highly efficient expression of chondroitin 4- O -sulfotransferase in Komagataella phaffii [J ] . Food and Fermentation Industries , 2026 , 52 ( 1 ): 1 - 10 .

OHTAKE S , ITO Y , FUKUTA M , et al . Human N -acetylgalactosamine 4-sulfate 6- O -sulfotransferase cDNA is related to human B cell recombination activating gene-associated gene [J ] . Journal of Biological Chemistry , 2001 , 276 ( 47 ): 43894 - 43900 .

OHTAKE S , KIMATA K , HABUCHI O . Recognition of sulfation pattern of chondroitin sulfate by uronosyl 2- O -sulfotransferase [J ] . Journal of Biological Chemistry , 2005 , 280 ( 47 ): 39115 - 39123 .

XU D , SONG D Y , PEDERSEN L C , et al . Mutational study of heparan sulfate 2- O -sulfotransferase and chondroitin sulfate 2- O -sulfotransferase [J ] . Journal of Biological Chemistry , 2007 , 282 ( 11 ): 8356 - 8367 .

LI J E , SU G W , LIU J . Enzymatic synthesis of homogeneous chondroitin sulfate oligosaccharides [J ] . Angewandte Chemie International Edition , 2017 , 56 ( 39 ): 11784 - 11787 .

JU R B , HAN B Q , HAN F , et al . Efficient expression and characterization of an endo-type lyase HCLase_M28 and its gradual scale-up fermentation for the preparation of chondroitin sulfate oligosaccharides [J ] . Applied Biochemistry and Biotechnology , 2024 , 196 ( 9 ): 6526 - 6555 .

HONDA T , KANEIWA T , MIZUMOTO S , et al . Hyaluronidases have strong hydrolytic activity toward chondroitin 4-sulfate comparable to that for hyaluronan [J ] . Biomolecules , 2012 , 2 ( 4 ): 549 - 563 .

FAN X M , ZHOU L J , HUANG J Y , et al . The structures and applications of microbial chondroitin AC lyase [J ] . World Journal of Microbiology & Biotechnology , 2022 , 38 ( 11 ): 199 .

HAMAI A , HASHIMOTO N , MOCHIZUKI H , et al . Two distinct chondroitin sulfate ABC lyases. An endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides [J ] . The Journal of Biological Chemistry , 1997 , 272 ( 14 ): 9123 - 9130 .

YIN F X , WANG F S , SHENG J Z . Uncovering the catalytic direction of chondroitin AC exolyase [J ] . Journal of Biological Chemistry , 2016 , 291 ( 9 ): 4399 - 4406 .

SUGAHARA K , TANAKA Y , YAMADA S . Preparation of a series of sulfated tetrasaccharides from shark cartilage chondroitin sulfate D using testicular hyaluronidase and structure determination by 500 MHz 1 H NMR spectroscopy [J ] . Glycoconjugate Journal , 1996 , 13 ( 4 ): 609 - 619 .

KANEIWA T , MIZUMOTO S , SUGAHARA K , et al . Identification of human hyaluronidase-4 as a novel chondroitin sulfate hydrolase that preferentially cleaves the galactosaminidic linkage in the trisulfated tetrasaccharide sequence [J ] . Glycobiology , 2010 , 20 ( 3 ): 300 - 309 .

WANG H , ZHANG L , ZHANG W J , et al . Secretory expression of biologically active chondroitinase ABC Ⅰ for production of chondroitin sulfate oligosaccharides [J ] . Carbohydrate Polymers , 2019 , 224 : 115135 .

CALLAWAY E . AI protein-prediction tool AlphaFold3 is now more open [J ] . Nature , 2024 , 635 ( 8039 ): 531 - 532 .

CHEN L T , LI Q M , NASIF K F A , et al . AI-driven deep learning techniques in protein structure prediction [J ] . International Journal of Molecular Sciences , 2024 , 25 ( 15 ): 8426 .

WU B H , ZHONG B , ZHENG L R , et al . Harnessing protein language model for structure-based discovery of highly efficient and robust PET hydrolases [J ] . Nature Communications , 2025 , 16 : 6211 .

ALBANESE K I , PETRENAS R , PIRRO F , et al . Rationally seeded computational protein design of ɑ-helical barrels [J ] . Nature Chemical Biology , 2024 , 20 ( 8 ): 991 - 999 .

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