Characterization of Methyltransferase AlmCII in Chalcomycin Biosynthesis: The First TylF Family O-Methyltransferase Works on a 4′-Deoxysugar
| Autor: | Chuan-Xi Wang, Hao Gao, Guo-Dong Chen, Dan Hu, Xiao-Long Tang, Kui Hong, Ping Dai, Xin-Sheng Yao, Qiao-Zhen Wang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Staphylococcus aureus Glycosylation Methyltransferase Cations Divalent Methylation Biochemistry Divalent 03 medical and health sciences chemistry.chemical_compound Biosynthesis Deoxy Sugars Magnesium Sugar Molecular Biology chemistry.chemical_classification biology Organic Chemistry Methyltransferases O-methyltransferase Anti-Bacterial Agents 030104 developmental biology Enzyme chemistry biology.protein Molecular Medicine Macrolides Antibacterial activity |
| Zdroj: | ChemBioChem. 18:1510-1517 |
| ISSN: | 1439-4227 |
| DOI: | 10.1002/cbic.201700216 |
| Popis: | Sugar O-methylation is a ubiquitous modification in natural products and plays diverse roles. This realization has inspired many attempts to search for novel methyltransferases. Chalcomycins are a group of 16-membered macrolides containing two methylated sugars that require three methyltransferases for their biosynthesis. Here, we identified that AlmCII, a sugar O-methyltransferase belonging to the TylF family that was previously only known to methylate sugars with a 4'-hydroxy group, can methylate a 4',6'-dideoxysugar during the biosynthesis of chalcomycins. An in vitro enzymatic assay revealed that AlmCII is divalent metal-dependent with an optimal pH of 8.0 and optimal temperature of 42 °C. Moreover, the 3'-O-demethylated chalcomycins exhibit less than 6 % of the antibacterial activity of their parent compounds. This is the first report demonstrating that a TylF family O-methyltransferase can use a 4'-deoxy sugar as a substrate and highlighting the importance of this methylation for the antibacterial activity of chalcomycins. |
| Databáze: | OpenAIRE |
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