valienol 1-phosphate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: valienol 1-phosphate
• 英文别名: Valienol 1-phosphate(2-)；[(1S,4R,5S,6R)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl] phosphate
• 化学式: C₇H₁₁O₈P
• 分子量: 254.133
• InChiKey: YLYKAEKEKWAWLH-VZFHVOOUSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  valienol 1-phosphate 在 recombinant cyclitol nucleotidyltransferase from Streptomyces hygroscopicus subsp. limoneus KCCM 11405 、 recombinant phosphatase from Streptomyces hygroscopicus subsp. limoneus KCCM 11405 、 recombinant pseudoglycosyltransferase from Streptomyces hygroscopicus subsp. limoneus KCCM 11405 、 valienol 1-phosphate 、 validamine 7-phosphate 、 Guanosine 5'-triphosphate 、 magnesium chloride 作用下， 反应 8.0h， 生成 4-(羟基甲基)-6-[[2,3,4-三羟基-5-(羟基甲基)环己基]氨基]环己-4-烯-1,2,3-三醇
  参考文献：
  名称：

  Pseudoglycosyltransferase Catalyzes Nonglycosidic C–N Coupling in Validamycin A Biosynthesis

  摘要：

  Glycosyltransferases are ubiquitous in nature. They catalyze a glycosidic bond formation between sugar donors and sugar or nonsugar acceptors to produce oligo/polysaccharides, glycoproteins, glycolipids, glycosylated natural products, and other sugar-containing entities. However, a trehalose 6-phosphate synthase-like protein has been found to catalyze an unprecedented nonglycosidic C-N bond formation in the biosynthesis of the aminocyclitol antibiotic validamycin A. This dedicated 'pseudoglycosyltransferase' catalyzes a condensation between GDP-valienol and validamine 7-phosphate to give validoxylamine A 7'-phosphate with net retention of the 'anomeric' configuration of the donor cyclitol in the product. The enzyme operates in sequence with a phosphatase, which dephosphorylates validoxylamine A 7'-phosphate to validoxylamine A.

  DOI：

  10.1021/ja203574u
• 作为试剂：
  描述：

  validamine 7-phosphate 在 recombinant cyclitol nucleotidyltransferase from Streptomyces hygroscopicus subsp. limoneus KCCM 11405 、 recombinant phosphatase from Streptomyces hygroscopicus subsp. limoneus KCCM 11405 、 recombinant pseudoglycosyltransferase from Streptomyces hygroscopicus subsp. limoneus KCCM 11405 、 valienol 1-phosphate 、 validamine 7-phosphate 、 Guanosine 5'-triphosphate 、 magnesium chloride 作用下， 反应 6.0h， 生成 4-(羟基甲基)-6-[[2,3,4-三羟基-5-(羟基甲基)环己基]氨基]环己-4-烯-1,2,3-三醇
  参考文献：
  名称：

  Pseudoglycosyltransferase Catalyzes Nonglycosidic C–N Coupling in Validamycin A Biosynthesis

  摘要：

  Glycosyltransferases are ubiquitous in nature. They catalyze a glycosidic bond formation between sugar donors and sugar or nonsugar acceptors to produce oligo/polysaccharides, glycoproteins, glycolipids, glycosylated natural products, and other sugar-containing entities. However, a trehalose 6-phosphate synthase-like protein has been found to catalyze an unprecedented nonglycosidic C-N bond formation in the biosynthesis of the aminocyclitol antibiotic validamycin A. This dedicated 'pseudoglycosyltransferase' catalyzes a condensation between GDP-valienol and validamine 7-phosphate to give validoxylamine A 7'-phosphate with net retention of the 'anomeric' configuration of the donor cyclitol in the product. The enzyme operates in sequence with a phosphatase, which dephosphorylates validoxylamine A 7'-phosphate to validoxylamine A.

  DOI：

  10.1021/ja203574u

文献信息

• Nucleotidylation of unsaturated carbasugar in validamycin biosynthesis
  作者：Jongtae Yang、Hui Xu、Yirong Zhang、Linquan Bai、Zixin Deng、Taifo Mahmud

  DOI：10.1039/c0ob00475h

  日期：——

  Validamycin A is a member of microbial-derived C7N-aminocyclitol family of natural products that is widely used as crop protectant and the precursor of the antidiabetic drug voglibose. Its biosynthetic gene clusters have been identified in several Streptomyces hygroscopicus strains, and a number of genes within the clusters have been functionally analyzed. Of these genes, valB, which encodes a sugar nucleotidyltransferase, was found through inactivation study to be essential for validamycin biosynthesis, but its role was unclear. To characterize the role of ValB in validamycin biosynthesis, four carbasugar phosphate analogues were synthesized and tested as substrate for ValB. The results showed that ValB efficiently catalyzes the conversion of valienol 1-phosphate to its nucleotidyl diphosphate derivatives, whereas other unsaturated carbasugar phosphates were found to be not the preferred substrate. ValB requires Mg2+, Mn2+, or Co2+ for its optimal activity and uses the purine-based nucleotidyltriphosphates (ATP and GTP) more efficiently than the pyrimidine-based NTPs (CTP, dTTP, and UTP) as nucleotidyl donor. ValB represents the first member of unsaturated carbasugar nucleotidyltransferases involved in natural products biosynthesis. Its characterization not only expands our understanding of aminocyclitol-derived natural products biosynthesis, but may also facilitate the development of new tools for chemoenzymatic synthesis of carbohydrate mimetics.

  Validamycin A 是源自微生物的 C7N-aminocyclitol 天然产物家族中的一员，被广泛用作作物保护剂和抗糖尿病药物伏格列波糖的前体。已在多个吸水链霉菌株中发现了其生物合成基因簇，并对基因簇中的一些基因进行了功能分析。在这些基因中，通过灭活研究发现编码糖核苷酸转移酶的 ValB 是有效霉素生物合成所必需的，但其作用尚不清楚。为了确定 ValB 在有效霉素生物合成中的作用，研究人员合成了四种碳糖磷酸类似物，并将其作为 ValB 的底物进行了测试。结果表明，ValB 能有效催化缬烯醇 1- 磷酸酯向其核苷酸二磷酸衍生物的转化，而其他不饱和碳糖磷酸酯并非其首选底物。ValB 需要 Mg2+、Mn2+ 或 Co2+ 才能达到最佳活性，它使用嘌呤型核苷酸三磷酸酯（ATP 和 GTP）作为核苷酸供体的效率要高于嘧啶型 NTP（CTP、dTTP 和 UTP）。ValB 是参与天然产物生物合成的不饱和碳糖核苷酸转移酶的第一个成员。对它的鉴定不仅拓展了我们对氨环糖醇衍生天然产物生物合成的了解，还有助于开发化学合成碳水化合物模拟物的新工具。