Abstract 2388 Examining a newly identified polysaccharide lyase family involved in glycosaminoglycans degradation

Glycosaminoglycans (GAGs) are long, linear, unbranched polysaccharides that have a negative charge and are made up of repeating disaccharide units that usually have an N-acetylated sugar and a uronic acid. GAG's structural diversity, combined with extensive interactions with a wide range of biological molecules, makes them important extracellular matrix (ECM) components that interact with a wide range of proteins involved in both normal physiological functions and disease-related processes. GAGs can undergo enzymatic depolymerization via specific carbohydrate-active enzymes, such as polysaccharide lyases (PLs). PLs are categorized into families based on amino acid sequence similarities. Although many of the PL families have been characterized, there are a number of families that have recently been identified, so their functions and roles within GAG metabolism are unclear. Notably certain bacterial strains possess a PL from the recently discovered PL family 33 (PL33) that is found in a distinctive gene cluster likely dedicated to GAG degradation. Here, we have performed bioinformatics, biochemical, and structural analyses to investigate these PL33 enzymes. We have determined that they act to break down both chondroitin sulfate and hyaluronic acid into unsaturated disaccharides, which would then enter the bacterium for further degradation by other enzymes from the gene cluster. This work sets the stage to validate our proposed novel GAG degradation pathway and further our understanding of newly identified carbohydrate-active enzyme families.