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Characterization of Methyltransferase AlmCII in Chalcomycin Biosynthesis: The First TylF Family O‐Methyltransferase Works on a 4′‐Deoxysugar
Author(s) -
Dai Ping,
Wang ChuanXi,
Gao Hao,
Wang QiaoZhen,
Tang XiaoLong,
Chen GuoDong,
Hong Kui,
Hu Dan,
Yao XinSheng
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700216
Subject(s) - methyltransferase , biosynthesis , o methyltransferase , methylation , biochemistry , transferase , enzyme , chemistry , divalent , substrate (aquarium) , stereochemistry , biology , organic chemistry , dna , ecology
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.