Article ; Online: Preference of Bacterial Rhamnosyltransferases for 6-Deoxysugars Reveals a Strategy To Deplete O-Antigens.
Journal of the American Chemical Society
2023 Volume 145, Issue 29, Page(s) 15639–15646
Abstract: Bacteria synthesize hundreds of bacteria-specific or "rare" sugars that are absent in mammalian cells and enriched in 6-deoxy monosaccharides such as l-rhamnose (l-Rha). Across bacteria, l-Rha is incorporated into glycans by rhamnosyltransferases (RTs) ... ...
| Abstract | Bacteria synthesize hundreds of bacteria-specific or "rare" sugars that are absent in mammalian cells and enriched in 6-deoxy monosaccharides such as l-rhamnose (l-Rha). Across bacteria, l-Rha is incorporated into glycans by rhamnosyltransferases (RTs) that couple nucleotide sugar substrates (donors) to target biomolecules (acceptors). Since l-Rha is required for the biosynthesis of bacterial glycans involved in survival or host infection, RTs represent potential antibiotic or antivirulence targets. However, purified RTs and their unique bacterial sugar substrates have been difficult to obtain. Here, we use synthetic nucleotide rare sugar and glycolipid analogs to examine substrate recognition by three RTs that produce cell envelope components in diverse species, including a known pathogen. We find that bacterial RTs prefer pyrimidine nucleotide-linked 6-deoxysugars, not those containing a C6-hydroxyl, as donors. While glycolipid acceptors must contain a lipid, isoprenoid chain length, and stereochemistry can vary. Based on these observations, we demonstrate that a 6-deoxysugar transition state analog inhibits an RT |
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| MeSH term(s) | O Antigens ; Bacteria/chemistry ; Glycolipids ; Sugars ; Nucleotides |
| Chemical Substances | O Antigens ; Glycolipids ; Sugars ; Nucleotides |
| Language | English |
| Publishing date | 2023-07-12 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 3155-0 |
| ISSN | 1520-5126 ; 0002-7863 |
| ISSN (online) | 1520-5126 |
| ISSN | 0002-7863 |
| DOI | 10.1021/jacs.3c03005 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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