Innovative insights on cleavage and hydrolysis mechanisms of hyaluronic acid: Opportunities and challenges in the preparation and application of hyaluronic acid and hyaluronidases

Hyaluronidase is used extensively across various domains, with food industry, healthcare, and surgical applications. Hyaluronidase produces low molecular weight hyaluronate through three mechanisms, substrate cleavage and two different hydrolysis pathways. Heterologous expression enhances the production of hyaluronidase in order to meet application demands. Several directed evolution strategies have been implemented to modify the properties of hyaluronidase. Hyaluronic acid of various molecular weights has been generated using metabolic engineering and enzyme engineering techniques. Both hyaluronidase and different Mw forms of hyaluronate have found widespread use in numerous fields. Although research on hyaluronidase and hyaluronic acid oligosaccharides faces opportunities and challenges, there are significant application prospects. This work underscores the potential for using hyaluronidase and hyaluronic acids of different Mw, with broad applicability and innovative prospects in bioresource exploration.