Enzymatic Production of Low-Molecular-Weight Hyaluronan and Its Oligosaccharides: A Review and Prospects

Abstract

Hyaluronic acid (HA) is a nonsulfated linear glycosaminoglycan with a negative charge. Different from the high-molecular-weight HAs, the low-molecular-weight HAs (LMW-HAs, 4–120 kDa) and hyaluronan oligosaccharides (O-HAs, <4 kDa) exhibit certain unique biological properties, owing to which these have a wide range of applications in the field of medicine. However, the chemical synthesis of high-purity LMW-HAs and O-HAs requires complex procedures, which renders this process difficult to achieve. The degradation of HA is achieved under the catalysis of hyaluronidases. In recent years, various hyaluronidase genes have been identified, and their enzymatic properties have been analyzed. In this context, the present review summarizes the hyaluronidases from different sources, which have been characterized. The review focuses on the crystal structure and the catalytic mechanism underlying the biological properties of hyaluronidases. In addition, the molecular weight distributions and the preparation approaches of the enzymatic products LMW-HAs and O-HAs are described. The general orientation of the research on hyaluronidases was speculated based on the existing literature. Accordingly, the efficient large-scale production of LMW-HAs and O-HAs using the green enzymatic approach was anticipated.

Hyaluronan – A multipotent biomolecule in the field of medicine

“…In vivo, the HAS catalyzes the conversion of nucleotide sugars UDP-GlcNAc and UDP-GlcUA to produce HA [11]. Class 1 HASs are less suitable for the production of HA as these enzymes are integral membrane proteins and research on these would require performance on membrane fraction, which is less suitable for largescale production [23]. Class 2 HASs produced by P. multocida are better enzymes for the production of HA; this enzyme has shown intracellular location when expressed in Escherichia coli [24].…”

Structural Analysis and Classification of Low-Molecular-Weight Hyaluronic Acid by Near-Infrared Spectroscopy: A Comparison between Traditional Machine Learning and Deep Learning

“…The acid degradation method has a high reaction and low cost, but it has the risk of destroying the basic disaccharide structural unit of HA, and there is residue, which poses a threat to human health [ 12 ]. The enzymatic hydrolysis has mild action and specific cleavage sites, which will not destroy the basic structure of HA [ 13 ]. Meanwhile, hyaluronidase as a natural ingredient is harmless to the human body [ 14 ], but a disadvantage is that the cost is high.…”