Construction of the Octose 8-Phosphate Intermediate in Lincomycin A Biosynthesis: Characterization of the Reactions Catalyzed by LmbR and LmbN,Journal of the American Chemical Society

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Construction of the Octose 8-Phosphate Intermediate in Lincomycin A Biosynthesis: Characterization of the Reactions Catalyzed by LmbR and LmbN
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2012-10-11 , DOI: 10.1021/ja308221z
Eita Sasaki ₁ , Chia-I Lin , Ke-Yi Lin , Hung-Wen Liu

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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 C(3) donor and D-ribose 5-phosphate as the C(5) acceptor. Subsequent 1,2-isomerization catalyzed by LmbN converts the resulting 2-keto C(8)-sugar (octulose 8-phosphate) to octose 8-phosphate. These results provide, for the first time, in vitro evidence for the biosynthetic origin of the C(8) backbone of MTL.

中文翻译：

林可霉素 A 生物合成中八糖八磷酸中间体的构建：LmbR 和 LmbN 催化反应的表征

林可霉素 A 是一种有效的抗菌剂，以其不寻常的 C1 甲基巯基取代的 8 碳糖而闻名。尽管其治疗革兰氏阳性菌感染的临床历史悠久，但对 C(8)-糖、甲基硫醇酰胺 (MTL) 的生物合成知之甚少。在这里，我们报告了我们对 MTL 生物合成途径中两个初始酶促步骤的研究，这些步骤导致将 D-赤型-D-葡萄糖-八糖八磷酸作为关键中间体的鉴定。我们的实验表明，该中间体是通过 LmbR 催化的转醛醇反应形成的，使用 D-果糖 6-磷酸或 D-sedoheptulose 7-磷酸作为 C(3) 供体和 D-核糖 5-磷酸作为 C(5) 受体. 随后由 LmbN 催化的 1,2-异构化将生成的 2-酮 C(8)-糖（8-磷酸八酮糖）转化为 8-磷酸八糖。这些结果提供，

更新日期：2012-10-11

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