Glycosaminoglycans (GAGs), as animal polysaccharides, are linked to proteins to form various types of proteoglycans. Bacterial GAG lyases are not only essential enzymes that spoilage bacteria use for the degradation of GAGs, but also valuable tools for investigating the biological function and potential therapeutic applications of GAGs. The ongoing discovery and characterization of novel GAG lyases has identified an increasing number of lyases suitable for functional studies and other applications involving GAGs, which include oligosaccharide sequencing, detection and removal of specific glycan chains, clinical drug development and the design of novel biomaterials and sensors, some of which have not yet been comprehensively summarized. GAG lyases can be classified into hyaluronate lyases, chondroitinases and heparinases based on their substrate spectra, and their functional applications are mainly determined by their substrates, with different lyases exhibiting differing substrate selectivity and preferences. It is thus necessary to understand the properties of the available enzymes to determine strategies for their functional application. Building on previous studies and reviews, this Review highlights small yet crucial differences among or within the various GAG lyases to aid in optimizing their use in future studies. To clarify ideas and strategies for further research, we also discuss several traditional and novel applications of GAG lyases.

Funding

Our work in this area was supported by the Natural Science Foundation of Shandong Province (nos. ZR2024MD015 and ZR2023MC017), National Key R&D Program of China (no. 2021YFC2103100), National Natural Science Foundation of China (nos. 31971201 and 31800665), Shandong Provincial Youth Innovation Science and Technology Support Program for Colleges and Universities (nos 2022RW088 and 2022KJ003), Major Scientific and Technology Innovation Project (MSTIP) of Shandong Province (no. 2019JZZY010817), and the SKLMT (State Key Laboratory of Microbial Technology, Shandong University) Frontiers and Challenges Project (SKLMTFCP-2023-06).

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