The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China; The Science Center for Future Foods, Jiangnan University, Wuxi 214122, China; The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China.
The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China; The Science Center for Future Foods, Jiangnan University, Wuxi 214122, China.
Int J Biol Macromol. 2023 Dec 31;253(Pt 1):126551. doi: 10.1016/j.ijbiomac.2023.126551. Epub 2023 Sep 1.
Chondroitin sulfate (CS) is a member of glycosaminoglycans (GAGs) and has critical physiological functions. CS is widely applied in medical and clinical fields. Currently, the supply of CS relies on traditional animal tissue extraction methods. From the perspective of medical applications, the biggest drawback of animal-derived CS is its uncontrollable molecular weight and sulfonated patterns, which are key factors affecting CS activities. The advances of cell-free enzyme catalyzed systems and de novo biosynthesis strategies have paved the way to rationally regulate CS sulfonated pattern and molecular weight. In this review, we first present a general overview of biosynthesized CS and its oligosaccharides. Then, the advances in chondroitin biosynthesis, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) synthesis and regeneration, and CS biosynthesis catalyzed by sulfotransferases are discussed. Moreover, the progress of mining and expression of chondroitin depolymerizing enzymes for preparation of CS oligosaccharides is also summarized. Finally, we analyze and discuss the challenges faced in synthesizing CS and its oligosaccharides using microbial and enzymatic methods. In summary, the biotechnological production of CS and its oligosaccharides is a promising method in addressing the drawbacks associated with animal-derived CS and enabling the production of CS oligosaccharides with defined structures.
硫酸软骨素（CS）是糖胺聚糖（GAGs）的成员，具有重要的生理功能。CS 广泛应用于医学和临床领域。目前，CS 的供应依赖于传统的动物组织提取方法。从医学应用的角度来看，动物源性 CS 的最大缺点是其分子量和磺化模式不可控，这是影响 CS 活性的关键因素。无细胞酶催化系统和从头生物合成策略的进步为合理调节 CS 的磺化模式和分子量铺平了道路。在这篇综述中，我们首先介绍了生物合成的 CS 及其寡糖的一般概述。然后，讨论了 CS 生物合成、3'-磷酸腺苷-5'-磷酸硫酸（PAPS）合成和再生以及磺基转移酶催化的 CS 生物合成的进展。此外，还总结了用于制备 CS 寡糖的软骨素解聚酶的挖掘和表达的进展。最后，我们分析和讨论了使用微生物和酶方法合成 CS 及其寡糖所面临的挑战。总之，CS 及其寡糖的生物技术生产是解决动物源性 CS 缺点的有前途的方法，并能够生产具有定义结构的 CS 寡糖。
