Sugar methyltransferase

Gaisser S, Lill R, Wirtz G et al (2001) New erythromycin derivatives from Saccharopoly-spora erythraea using sugar O-methyltransferase from the spinosyn biosynthetic gene cluster. Mol Microbiol 41 1223-1231... 

The pseudorotationally constrained abasic site (55), based on bicyclo[3.1.0] hexane, has been incorporated into the methyltransferase M.Hhal recognition sequence to probe the mechanism of base flipping.Binding affinity increases when the abasic sugar is constrained to the north configuration, and is related to the ability of the abasic sugar to flip out of the DNA duplex. 

Examples for substrate ambiguity include enzymes such as sugar kinases, amino acid transferases, glycosi-dases, and methyltransferases, which can perform the same chemical transformation on substrates other than their native one (Table 1, entries 3-6). 

Methyl transfer reactions play a significant part in the modifications of aromatic polyketides, both of the polyketide core [61,62] as well as of several of the sugar moieties [44,53]. In Streptomyces, more than 20 amino acid sequences have been found that may represent enzymes involved in methyl transfer reactions in the biosynthesis of aromatic polyketides [149]. One of these enzymes, the S-adenosyl-L-methionine-dependent DnrK, is involved in the methylation of the C-4 hydroxyl group in daunorubicin/doxorubicin biosynthesis (Scheme 10, step 12). The subunit of the homo-dimeric enzyme displays a fold typical for small-molecule methyltransferases. The structure of the ternary complex with bound products S-adenosyl-L-homocysteine and 4-methoxy-8-rhodomycin provided insights into the structural basis of substrate recognition and catalysis [149]. The position and orientation of the substrates suggest an Sn2 mechanism for methyl transfer, and mutagenesis experiments show that there is no catalytic base in the vicinity of the substrate. Rate enhancement is thus most likely due to orientational and proximity effects [149]. 

The methyl group attached to the 5-OH arises by transfer of the methyl of S-adenosylmethionine catalyzed by a specific 0-methyltransferase [21]. A specific 5-ketoreductase has been shown to convert 5-keto avermectins into the B components [22]. The glycosyltransferase which catalyzes the stepwise transfer of oleandrose from thymidine diphosphate oleandrose to the aglycone has been demonstrated in cell free extracts [23]. Whether the sugars are transferred sequentially is not clear. 

Polynudeotide-methyltransferase, polynucleotide methylases spedfic enzymes that catalyse the methylation of purine and pyrimidine bases, or sugars in the intact polynucleotide chain by transfer of methyl groups from S-adenosyl-L-methionine. 

---