3-O-mycarosylerythronolide B | 34698-88-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: 3-O-mycarosylerythronolide B
• 英文别名: 3-O-α-L-mycarosylerythronolide B；3-O-alpha-mycarosylerythronolide B；(3R,4S,5R,6R,7R,9R,11R,12S,13R,14R)-4-[(2R,4R,5S,6S)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-14-ethyl-6,7,12-trihydroxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione
• CAS: 34698-88-9
• 化学式: C₂₈H₅₀O₁₀
• 分子量: 546.699
• InChiKey: WWWXDCNRNMZGEN-UPOWUTDQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  38
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  163
• 氢给体数：
  5
• 氢受体数：
  10

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  14-乙基-4,6,7,12-四羟基-3,5,7,9,11,13-六甲基-1-氧杂环十四烷-2,10-二酮	erythronolide B	3225-82-9	C21H38O7	402.529

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	6-O-mycaminosyl erythromycin	25405-65-6	C37H67NO14	749.937

反应信息

• 作为反应物：
  描述：

  3-O-mycarosylerythronolide B 、 TDP-L-mycarose 在 Saccharopolyspora erythraea SGQ₂/pSGeryCIII BIOT-2191 作用下， 以 甲醇 为溶剂， 以15.8%的产率得到3,5-bis-O-α-L-mycarosylerythronolide B
  参考文献：
  名称：

  Engineered biosynthesis of hybrid macrolide polyketides containing d-angolosamine and d-mycaminose moieties

  摘要：

  天然产物框架的糖基化，尤其是高度修饰的脱氧糖，通常对其生物活性至关重要，负责与分子靶点的特定接触，并显著影响其药代动力学特性。为了提供针对天然产物糖基化模式的目标性改变的工具，已经在理解活化脱氧糖的生物合成及其转移方面取得了重要进展。我们在这里报告了制作质粒载体生物合成基因盒的努力，这些盒子能够生产TDP-活化形式的D-美卡硫糖、D-安哥洛糖和D-脱硫糖。同时，我们还描述了利用糖基转移酶EryCIII、TylMII和AngMII将这些脱氧糖转移到大环甾烯的工作，这些转移酶显示出有用的广谱底物耐受性。

  DOI：

  10.1039/b807914e
• 作为产物：
  描述：

  dTDP-beta-L-mycarose(2-) 、 14-乙基-4,6,7,12-四羟基-3,5,7,9,11,13-六甲基-1-氧杂环十四烷-2,10-二酮 生成 3-O-mycarosylerythronolide B 、 TMP 、 氢(+1)阳离子
  参考文献：
  名称：

  赤藓醇内酰胺基转移酶EryBV的体外表征及其在大环内酯多样化中的应用。

  摘要：

  DOI：

  10.1002/cbic.200600509

文献信息

• In Vitro Reconstitution of EryCIII Activity for the Preparation of Unnatural Macrolides
  作者：Yanqiu Yuan、Hak Suk Chung、Catherine Leimkuhler、Christopher T. Walsh、Daniel Kahne、Suzanne Walker

  DOI：10.1021/ja053704n

  日期：2005.10.1

  EryCIII is a desosaminyltransferase that converts an inactive macrolide precursor to a biologically active antibiotic. It may have potential for the synthesis of unnatural macrolides with useful biological activities. However, it has been difficult to reconstitute the activity of EryCIII in vitro. We report here that purified, inactive EryCIII can be converted to an active catalyst by the addition of another protein encoded in the same gene cluster, EryCII. The EryCII-treated protein retains activity even when EryCII is removed. We also show that AknT, an activator protein from an unrelated gene cluster, is capable of activating EryCIII. Although the mechanism of activation is not yet understood, we have concluded from these experiments that these antibiotic Gtf activator proteins do not function to deliver substrates to EryCIII and do not exert their effects by forming stable complexes with the Gtf during the glycosyltransfer reaction. We report that activated EryCIII is capable of utilizing an alternative sugar donor, so these results lay the groundwork for the production of novel macrolides.
• Reconstitution and Characterization of a New Desosaminyl Transferase, EryCIII, from the Erythromycin Biosynthetic Pathway
  作者：Ho Young Lee、Hak Suk Chung、Chao Hang、Chaitan Khosla、Christopher T. Walsh、Daniel Kahne、Suzanne Walker

  DOI：10.1021/ja048836f

  日期：2004.8.1

  EryCIII converts alpha-mycarosyl erythronolide B into erythromycin D using TDP-d-desosamine as the glycosyl donor. We report the heterologous expression, purification, in vitro reconstitution, and preliminary characterization of EryCIII. Coexpression of EryCIII with the GroEL/ES chaperone complex was found to enhance greatly the expression of soluble EryCIII protein. The enzyme was found to be highly active with a kcat greater than 100 min-1. EryCIII was quite selective for the natural nucleotide sugar donor and macrolide acceptor substrates, unlike several other antibiotic glycosyl transferases with broad specificity such as desVII, oleG2, and UrdGT2. Within detectable limits, neither 6-deoxyerythronolide B nor 10-deoxymethynolide were found to be glycosylated by EryCIII. Furthermore, TDP-d-mycaminose, which only differs from TDP-d-desosamine at the C4 position, could not be transferred to alphaMEB. These studies lay the groundwork for detailed structural and mechanistic analysis of an important member of the desosaminyl transferase family of enzymes.
• Engineered biosynthesis of hybrid macrolide polyketides containing d-angolosamine and d-mycaminose moieties
  作者：Ursula Schell、Stephen F. Haydock、Andrew L. Kaja、Isabelle Carletti、Rachel E. Lill、Eliot Read、Lesley S. Sheehan、Lindsey Low、Maria-Jose Fernandez、Friederike Grolle、Hamish A. I. McArthur、Rose M. Sheridan、Peter F. Leadlay、Barrie Wilkinson、Sabine Gaisser

  DOI：10.1039/b807914e

  日期：——

  The glycosylation of natural product scaffolds with highly modified deoxysugars is often essential for their biological activity, being responsible for specific contacts to molecular targets and significantly affecting their pharmacokinetic properties. In order to provide tools for the targeted alteration of natural product glycosylation patterns, significant strides have been made to understand the biosynthesis of activated deoxysugars and their transfer. We report here efforts towards the production of plasmid-borne biosynthetic gene cassettes capable of producing TDP-activated forms of D-mycaminose, D-angolosamine and D-desosamine. We additionally describe the transfer of these deoxysugars to macrolide aglycones using the glycosyl transferases EryCIII, TylMII and AngMII, which display usefully broad substrate tolerance.

  天然产物框架的糖基化，尤其是高度修饰的脱氧糖，通常对其生物活性至关重要，负责与分子靶点的特定接触，并显著影响其药代动力学特性。为了提供针对天然产物糖基化模式的目标性改变的工具，已经在理解活化脱氧糖的生物合成及其转移方面取得了重要进展。我们在这里报告了制作质粒载体生物合成基因盒的努力，这些盒子能够生产TDP-活化形式的D-美卡硫糖、D-安哥洛糖和D-脱硫糖。同时，我们还描述了利用糖基转移酶EryCIII、TylMII和AngMII将这些脱氧糖转移到大环甾烯的工作，这些转移酶显示出有用的广谱底物耐受性。
• The In Vitro Characterization of the Erythronolide Mycarosyltransferase EryBV and Its Utility in Macrolide Diversification
  作者：Changsheng Zhang、Qiang Fu、Christoph Albermann、Lingjun Li、Jon S. Thorson

  DOI：10.1002/cbic.200600509

  日期：2007.3.5