2'-[O-(β-D-glucopyranosyl)]erythromycin A

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2'-[O-(β-D-glucopyranosyl)]erythromycin A
• 英文别名: (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione
• 化学式: C₄₃H₇₇NO₁₈
• 分子量: 896.08
• InChiKey: UIKGILYUUGQGIC-QPTLJKIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  62
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  273
• 氢给体数：
  8
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  尿苷(5')二氢二磷酰(1)-alpha-D-葡萄糖 、 红霉素 在 magnesium 作用下， 以20 mg的产率得到2'-[O-(β-D-glucopyranosyl)]erythromycin A
  参考文献：
  名称：

  Microbial Glycosylation of Macrolide Antibiotics by Streptomyces hygroscopicus ATCC 31080 and Distribution of a Macrolide Glycosyl Transferasein Several Streptomyces Strains.

  摘要：

  在我们的红霉素衍生物微生物转化研究过程中，发现能够产生聚醚类抗生素Carriomycin的Streptomyces hygroscopicus ATCC 31080可以将红霉素衍生物转化为失活衍生物。通过分析这些失活衍生物的光谱数据，阐明了利用细胞提取物、UDP-葡萄糖（或UDP-半乳糖）和Mg2+（或Mn2+）进行酶反应制备的失活衍生物的结构，确认它们是在脱氧胺部分的C-2'位上进行了糖基化的化合物，表明该酶是一种大环内酯糖基转移酶（MGT）。从产生竹桃霉素的S. antibioticus ATCC 11891中提取的细胞提取物的MGT活性，可以根据其对泰乐菌素的糖基化能力与ATCC 31080区分开来。我们检测了32株产生大环内酯和聚醚类抗生素等多酮化合物的放线菌菌株，发现其中15株链霉菌具有大环内酯糖基转移酶活性。这表明MGTs至少在产生多酮化合物的链霉菌菌株中分布广泛。

  DOI：

  10.7164/antibiotics.49.1110

文献信息

• A β-(1,2)-Glycosynthase and an Attempted Selection Method for the Directed Evolution of Glycosynthases
  作者：David L. Jakeman、Ali Sadeghi-Khomami

  DOI：10.1021/bi201438q

  日期：2011.11.29

  reprogramming for biotechnological applications. The family 3 retaining glycosidase postulated to be involved in erythromycin self-resistance was cloned, recombinantly expressed in Escherichia coli, purified, and characterized. Bioinformatics analysis allowed the identification of the acid/base and nucleophile residues, and mutation of these residues resulted in hydrolytically inactive proteins. One mutant

  了解酶如何介导催化作用是将其重新编程用于生物技术应用的关键。克隆假定与红霉素自身抗性有关的家族3保留糖苷酶，在大肠杆菌中重组表达，纯化和表征。生物信息学分析允许鉴定酸/碱和亲核残基，并且这些残基的突变导致水解失活的蛋白质。一个突变体能够使用α-葡萄糖基氟化物作为供体和大环内酯类抗生素作为受体来合成糖苷键。这显示了糖合酶技术在完成具有挑战性的氨基糖的β-（1,2）-糖基化方面的空前应用。这项工作还提供了EryBI蛋白的第一个生化特性，并支持了它在红霉素生物合成中涉及的自耐药机制中的作用。为了刺激糖合酶的进化，使用了体内选择方法，
• Probing the Breadth of Macrolide Glycosyltransferases:  In Vitro Remodeling of a Polyketide Antibiotic Creates Active Bacterial Uptake and Enhances Potency
  作者：Min Yang、Mark R. Proctor、David N. Bolam、James C. Errey、Robert A. Field、Harry J. Gilbert、Benjamin G. Davis

  DOI：10.1021/ja051482n

  日期：2005.7.1

  The glycan portion of macrolide antibiotics modulates their efficacy. High-level expression of three macrolide GTs and kinetic analysis has revealed a highly selective synthetic "tool kit" with such plasticity that 12 glycan-modified macrolide antibiotics have been readily created. One of these (1-Gal) is enhanced over its parent oleandomycin (1) by "glycotargeting", allowing higher uptake through active internalization by virtue of the attachment of a glycan (Gal) not normally found on 1. Subsequent release of the targeting glycan by endogenous galactosidase activity releases 1.
• Microbial Glycosylation of Macrolide Antibiotics by Streptomyces hygroscopicus ATCC 31080 and Distribution of a Macrolide Glycosyl Transferasein Several Streptomyces Strains.
  作者：Jon SASAKI、KAZUTOSHI MIZOUE、SHIGEO MORIMOTO、SADAFUMI OMURA

  DOI：10.7164/antibiotics.49.1110

  日期：——

  In the course of our microbial transformation study on erythromycin derivatives, Streptomyces hygroscopicus ATCC 31080, which produces a poly ether antibiotic carriomycin, was found to transform erythromycin derivatives to their inactivated derivatives. The structures of inactivated derivatives prepared by enzyme reaction using the cell extract, UDP-glucose (or UDP-galactose) and Mg2+ (or Mn2+) were elucidated on the basis of analysis of their spectral data to be the compounds glycosylated at C-2' of a desosamine moiety, indicating that the enzyme is a macrolide glycosyl transferase (MGT). The MGT activity of cell extract from S. antibiotieus ATCC 11891, a producing organism of oleandomycin, could be distinguished from that of ATCC 31080, based on the ability to glycosylate tylosin. We examined 32 actinomycete strains producing such polyketides as macrolide and polyether antibiotics, and found that 15 strains of Streptomyces have macrolide glycosyl transferase activity. It suggests that the MGTs have been distributed among at least polyketide producing Streptomyces strains.

  在我们的红霉素衍生物微生物转化研究过程中，发现能够产生聚醚类抗生素Carriomycin的Streptomyces hygroscopicus ATCC 31080可以将红霉素衍生物转化为失活衍生物。通过分析这些失活衍生物的光谱数据，阐明了利用细胞提取物、UDP-葡萄糖（或UDP-半乳糖）和Mg2+（或Mn2+）进行酶反应制备的失活衍生物的结构，确认它们是在脱氧胺部分的C-2'位上进行了糖基化的化合物，表明该酶是一种大环内酯糖基转移酶（MGT）。从产生竹桃霉素的S. antibioticus ATCC 11891中提取的细胞提取物的MGT活性，可以根据其对泰乐菌素的糖基化能力与ATCC 31080区分开来。我们检测了32株产生大环内酯和聚醚类抗生素等多酮化合物的放线菌菌株，发现其中15株链霉菌具有大环内酯糖基转移酶活性。这表明MGTs至少在产生多酮化合物的链霉菌菌株中分布广泛。