Microbial synthesis of glycosaminoglycans and their oligosaccharides

Compared with chemical synthesis and tissue extraction methods, microbial synthesis of glycosaminoglycans (GAGs) is attractive because of the advantages of eco-friendly processes, production safety, and sustainable development. However, boosting the efficiency of microbial cell factories, precisely regulating GAG molecular weights, and rationally controlling the sulfation degree of GAGs remain challenging. To address these issues, various strategies, including genetic, enzymatic, metabolic, and fermentation engineering, have been developed. In this review, we summarize the recent progress in the construction of efficient GAG-producing microbial cell factories, regulation of the molecular weight of GAGs, and modification of GAG chains. Moreover, future studies, remaining challenges, and potential solutions in this field are discussed. Various microorganisms have been constructed to efficiently synthesize glycosaminoglycans (GAGs) and their oligosaccharides, which are considered to be the most promising alternative to traditional tissue extraction methods.Microorganisms can synthesize GAGs with a wide range of molecular weights (MWs) by regulating precursor supply, enzyme activity, and the extracellular microenvironment.Different types of synthetases and modifying enzymes were expressed in microorganisms, which paved the way for the synthesis and modification of GAGs by microorganisms.The one-step microbial production of chondroitin sulfate and heparin marks an important step in the animal-free production of sulfated GAGs.