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Title: | REWIRING THE PNEUMOCOCCAL CAPSULE PATHWAY FOR INVESTIGATING GLYCOSYLTRANSFERASE SPECIFICITY AND GENETIC GLYCOENGINEERING. | Authors: | SU TONG | ORCID iD: | ![]() |
Keywords: | Streptococcus pneumoniae, glycosyltransferases, glycoengineering, capsular polysaccharides, glycans, glycosidic linkages | Issue Date: | 2-Nov-2023 | Citation: | SU TONG (2023-11-02). REWIRING THE PNEUMOCOCCAL CAPSULE PATHWAY FOR INVESTIGATING GLYCOSYLTRANSFERASE SPECIFICITY AND GENETIC GLYCOENGINEERING.. ScholarBank@NUS Repository. | Abstract: | Glycans and glycoconjugates are present in all living cells. Their structures are primarily controlled by the specificities of glycosyltransferases (GTs). GTs typically adopt one of the three folds: GT-A, GT-B, and GT-C. However, what defines their specificities remains poorly understood. Here, we reported a genetic glycoengineering approach to reprogram capsular polysaccharide pathways in Streptococcus pneumoniae to investigate GT specificity and manipulate glycan structures. Our findings suggest that the central cleft of GT-B enzymes is important for determining acceptor specificity. Mutations in glycosyltransferases and transporters partially alleviated constraints of the glycoengineering platform to relax substrate specificity or through biochemical derivatization of purified glycans. We also modified the pneumococcal capsule to produce several medically important mammalian glycans, as well as demonstrated the importance of regiochemistry in a glycosidic linkage on binding lung epithelial cells. Our work provided mechanistic insights into GT specificity and an approach for investigating glycan functions. | URI: | https://scholarbank.nus.edu.sg/handle/10635/248152 |
Appears in Collections: | Ph.D Theses (Open) |
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