Construction of the octose 8-phosphate intermediate in lincomycin A biosynthesis: Characterization of the reactions catalyzed by LmbR and LmbN

Eita Sasaki, Chia I. Lin, Ke Yi Lin, Hung Wen Liu

研究成果: Article査読

40 被引用数 (Scopus)

抄録

Lincomycin A is a potent antimicrobial agent noted for its unusual C1 methylmercapto-substituted 8-carbon sugar. Despite its long clinical history for the treatment of Gram-positive infections, the biosynthesis of the C 8-sugar, methylthiolincosamide (MTL), is poorly understood. Here, we report our studies of the two initial enzymatic steps in the MTL biosynthetic pathway leading to the identification of d-erythro-d-gluco-octose 8-phosphate as a key intermediate. Our experiments demonstrate that this intermediate is formed via a transaldol reaction catalyzed by LmbR using d-fructose 6-phosphate or d-sedoheptulose 7-phosphate as the C3 donor and d-ribose 5-phosphate as the C5 acceptor. Subsequent 1,2-isomerization catalyzed by LmbN converts the resulting 2-keto C8-sugar (octulose 8-phosphate) to octose 8-phosphate. These results provide, for the first time, in vitro evidence for the biosynthetic origin of the C8 backbone of MTL.

本文言語English
ページ(範囲)17432-17435
ページ数4
ジャーナルJournal of the American Chemical Society
134
42
DOI
出版ステータスPublished - 2012 10月 24
外部発表はい

ASJC Scopus subject areas

  • 触媒
  • 化学一般
  • 生化学
  • コロイド化学および表面化学

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