Advances and challenges in biotechnological production of chondroitin sulfate and its oligosaccharides

Int J Biol Macromol. 2023 Dec 31;253(Pt 1):126551. doi: 10.1016/j.ijbiomac.2023.126551. Epub 2023 Sep 1.

Abstract

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.

Keywords: 3′-Phosphoadenosine-5′-phosphosulfate; Chondroitin sulfate; Glycosaminoglycan; Oligosaccharides; Sulfotransferases.

Publication types

  • Review

MeSH terms

  • Animals
  • Biotechnology
  • Chondroitin Sulfates* / chemistry
  • Glycosaminoglycans / chemistry
  • Oligosaccharides* / chemistry

Substances

  • Chondroitin Sulfates
  • Oligosaccharides
  • Glycosaminoglycans