Glycosylation of Acyclic and Cyclic Aglycone Substrates by Macrolide Glycosyltransferase DesVII/DesVIII: Analysis and Implications
✍ Scribed by Svetlana A. Borisova; Hak Joong Kim; Xiaotao Pu; Hung-wen Liu
- Book ID
- 101817763
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 256 KB
- Volume
- 9
- Category
- Article
- ISSN
- 1439-4227
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✦ Synopsis
Macrolides target the bacterial protein translation machinery and are one of the most prescribed classes of antibiotics to treat bacterial infection. [1] However, emerging bacterial resistance to macrolides necessitates the development of new analogues that can potentially be used as drugs. The structures of macrolides are characterized by a macrolactone, which is commonly glycosylated with one or more deoxysugars. [1] Extensive experiments revealed a relaxed specificity of the responsible macrolide glycosyltransferases (GTs) toward both the sugar and aglycone substrates. [3] Thus, exploiting the catalytic flexibility of these GTs offers an attractive means for creating new macrolide derivatives. [2] Among the growing number of in vitro studies of related GTs, DesVII, which catalyzes the attachment of d-desosamine (1) to 10-deoxymethynolide (2) or narbonolide (3) in the biosynthesis of methymycin (6), neomethymycin (7), narbomycin (5), and pikromycin (8) in Streptomyces venezuelae, is one of the most extensively studied macrolide GTs (Scheme 1). [3d, 4] Previous studies showed that DesVII needs an auxiliary protein, DesVIII, for in vitro activity. [4a, 5] The detailed in vitro analysis of sugar substrate specificity of DesVII/DesVIII had been carried
[a] Dr.