Characterization of Methyltransferase AlmCII in Chalcomycin Biosynthesis: The First TylF Family O-Methyltransferase Works on a 4′-Deoxysugar

5 years ago

Characterization of Methyltransferase AlmCII in Chalcomycin Biosynthesis: The First TylF Family O-Methyltransferase Works on a 4′-Deoxysugar

Qiao-Zhen Wang, Kui Hong, Dan Hu, Guo-Dong Chen, Xin-Sheng Yao, Xiao-Long Tang, Chuan-Xi Wang, Ping Dai, Hao Gao

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. Gimme some sugar! AlmCII is the first example of an O-methyltransferase from the TylF family that can use a 4′-deoxysugar as a substrate, catalyzing the 3′-O-methylation of a 4,6-dideoxysugar to form the chalcose moiety during the biosynthesis of chalcomycins. This modification contributes significantly to the antibacterial activity of chalcomycins.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/cbic.201700216