dTDP-2,3-dehydro-2,6-dideoxy-4-keto-alpha-D-glucose(2-)

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: dTDP-2,3-dehydro-2,6-dideoxy-4-keto-alpha-D-glucose(2-)
• 英文别名: [[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphoryl] [(2R,6R)-4-hydroxy-6-methyl-5-oxo-2H-pyran-2-yl] phosphate
• 化学式: C16H20N2O14P2-2
• 分子量: 526.28
• InChiKey: QWDIAMULKXKCNE-NJIBTWPXSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  233
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  dTDP-2,3-dehydro-2,6-dideoxy-4-keto-alpha-D-glucose(2-) 生成 dTDP-3,4-didehydro-2,6-dideoxy-alpha-D-glucose(2-)
  参考文献：
  名称：

  夹竹桃霉素生产者抗生素链霉菌中参与 L-夹竹桃糖及其中间体 L-橄榄糖生物合成的基因的鉴定和表达。

  摘要：

  克隆了来自抗生素链霉菌中夹竹桃霉素基因簇的 9.8-kb DNA 区域。序列分析揭示了 8 个开放阅读框的存在，它们编码参与连接到夹竹桃霉素糖苷配基上的两种 2, 6-脱氧糖之一的生物合成中的不同酶活性：L-夹竹桃糖（oleW、oleV、oleL 和 oleU 基因）和D-去糖胺（oleNI 和 oleT 基因），或两者兼有（oleS 和 oleE 基因）。构建了含有整合到染色体中的oleG2糖基转移酶基因的白色链霉菌菌株。该菌株用两种不同的质粒构建体（pOLV 和 pOLE）转化，这些质粒构建体分别含有一组被认为是 dTDP-L-橄榄糖和 dTDP-L-夹竹桃糖生物合成所需的基因。将这些重组菌株与红霉素苷元（erythronolide B）一起孵育产生了两种新的糖基化化合物，分别为 L-3-O-olivosyl-和 L-3-O-oleandrosyl-erythronolide B，表明

  DOI：

  10.1128/aac.44.5.1266-1275.2000
• 作为产物：
  描述：

  TDP-4-keto-6-deoxy-D-glucose 生成 dTDP-2,3-dehydro-2,6-dideoxy-4-keto-alpha-D-glucose(2-) 、 水
  参考文献：
  名称：

  夹竹桃霉素生产者抗生素链霉菌中参与 L-夹竹桃糖及其中间体 L-橄榄糖生物合成的基因的鉴定和表达。

  摘要：

  克隆了来自抗生素链霉菌中夹竹桃霉素基因簇的 9.8-kb DNA 区域。序列分析揭示了 8 个开放阅读框的存在，它们编码参与连接到夹竹桃霉素糖苷配基上的两种 2, 6-脱氧糖之一的生物合成中的不同酶活性：L-夹竹桃糖（oleW、oleV、oleL 和 oleU 基因）和D-去糖胺（oleNI 和 oleT 基因），或两者兼有（oleS 和 oleE 基因）。构建了含有整合到染色体中的oleG2糖基转移酶基因的白色链霉菌菌株。该菌株用两种不同的质粒构建体（pOLV 和 pOLE）转化，这些质粒构建体分别含有一组被认为是 dTDP-L-橄榄糖和 dTDP-L-夹竹桃糖生物合成所需的基因。将这些重组菌株与红霉素苷元（erythronolide B）一起孵育产生了两种新的糖基化化合物，分别为 L-3-O-olivosyl-和 L-3-O-oleandrosyl-erythronolide B，表明

  DOI：

  10.1128/aac.44.5.1266-1275.2000

文献信息

• <i>In Vitro</i> Characterization of the Enzymes Involved in TDP-<scp>d</scp>-Forosamine Biosynthesis in the Spinosyn Pathway of <i>Saccharopolyspora </i><i>spinosa</i>
  作者：Lin Hong、Zongbao Zhao、Charles E. Melançon、Hua Zhang、Hung-wen Liu

  DOI：10.1021/ja0771383

  日期：2008.4.1

  6-tetradeoxy-beta-D-threo-hexopyranose) is a highly deoxygenated sugar component of several important natural products, including the potent yet environmentally benign insecticide spinosyns. To study D-forosamine biosynthesis, the five genes (spnO, N, Q, R, and S) from the spinosyn gene cluster thought to be involved in the conversion of TDP-4-keto-6-deoxy-D-glucose to TDP-D-forosamine were cloned and heterologously

  Forosamine (4-二甲氨基)-2,3,4,6-tetradeoxy-beta-D-threo-hexopyranose) 是几种重要天然产物的高度脱氧糖成分，包括强效但对环境无害的杀虫剂多杀菌素。为了研究 D-forosamine 生物合成，来自多杀菌素基因簇的五个基因（spnO、N、Q、R 和 S）被认为参与了 TDP-4-keto-6-deoxy-D-葡萄糖向 TDP 的转化-D-forosamine 被克隆并异源表达，相应的蛋白质被纯化并在体外检查它们的活性。先前的工作表明，SpnQ 作为一种依赖于 5'-单磷酸酯 (PMP) 的 3-脱水酶，在细胞还原酶对铁氧还蛋白/铁氧还蛋白还原酶或黄素氧还蛋白/黄素氧还蛋白还原酶存在的情况下，催化 TDP-4 的 C-3 脱氧-keto-2,6-dideoxy-D-葡萄糖。还确定 SpnR 作为转氨酶发挥作用，将 SpnQ 产物 TDP-4-keto-2
• TDP- <scp>l</scp> -Megosamine Biosynthesis Pathway Elucidation and Megalomicin A Production in <i>Escherichia coli</i>
  作者：Mariana Useglio、Salvador Peirú、Eduardo Rodríguez、Guillermo R. Labadie、John R. Carney、Hugo Gramajo

  DOI：10.1128/aem.03083-09

  日期：2010.6.15

  In vivo reconstitution of the TDP-l-megosamine pathway from the megalomicin gene cluster of Micromonospora megalomicea was accomplished by the heterologous expression of its biosynthetic genes in Escherichia coli. Mass spectrometric analysis of the TDP-sugar intermediates produced from operons containing different sets of genes showed that the production of TDP-l-megosamine from TDP-4-keto-6-deoxy-d-glucose

  来自 Micromonospora megalomicea 的 megalomicin 基因簇的 TDP-l-megosamine 途径的体内重建是通过其生物合成基因在大肠杆菌中的异源表达来完成的。对由含有不同基因组的操纵子产生的 TDP-糖中间体的质谱分析表明，从 TDP-4-keto-6-deoxy-d-glucose 产生 TDP-1-megosamine 只需要五个生物合成步骤，由 MegBVI 催化、MegDII、MegDIII、MegDIV 和 MegDV。生物转化研究表明，糖转移酶 MegDI 与辅助蛋白 MegDVI 一起催化 l-甲基氨基葡萄糖向红霉素 C 或红霉素 D 的转移，表明产生巨霉素 A 的两种可能途径。
• Biosynthesis of the dideoxysugar component of jadomycin B: genes in the jad cluster of Streptomyces venezuelae ISP5230 for l-digitoxose assembly and transfer to the angucycline aglycone The GenBank accession number for the sequence reported in this paper is AY026363.
  作者：Liru Wang、Robert L. White、Leo C. Vining

  DOI：10.1099/00221287-148-4-1091

  日期：2002.4.1

  Eight additional genes, jadX, O, P, Q, S, T, U and V, in the jad cluster of Streptomyces venezuelae ISP5230, were located immediately downstream of jadN by chromosome walking. Sequence analyses and comparisons implicated them in biosynthesis of the 2,6-dideoxysugar in jadomycin B. The genes were cloned in Escherichia coli, inactivated by inserting an apramycin resistance cassette with a promoter driving transcription of downstream genes, and transferred into Streptomyces venezuelae by intergeneric conjugation. Analysis by HPLC and NMR of intermediates accumulated by cultures of the insertionally inactivated Streptomyces venezuelae mutants indicated that jadO, P, Q, S, T, U and V mediate formation of the dideoxysugar moiety of jadomycin B and its attachment to the aglycone. Based on these results and sequence similarities to genes described in other species producing deoxysugar derivatives, a biosynthetic pathway is proposed in which the jadQ product (glucose-1-phosphate nucleotidyltransferase) activates glucose to its nucleotide diphosphate (NDP) derivative, and the jadT product (a 4,6-dehydratase) converts this to NDP-4-keto-6-deoxy-D-glucose. An NDP-hexose 2,3-dehydratase and an oxidoreductase, encoded by jadO and jadP, respectively, catalyse ensuing reactions that produce an NDP-2,6-dideoxy-D-threo-4-hexulose. The product of jadU (NDP-4-keto-2,6-dideoxy-5-epimerase) converts this intermediate to its L-erythro form and the jadV product (NDP-4-keto-2,6-dideoxyhexose 4-ketoreductase) reduces the keto group of the NDP-4-hexulose to give an activated form of the L-digitoxose moiety in jadomycin B. Finally, a glycosyltransferase encoded by jadS transfers the activated sugar to jadomycin aglycone. The function of jadX is unclear; the gene is not essential for jadomycin B biosynthesis, but its presence ensures complete conversion of the aglycone to the glycoside. The deduced amino acid sequence of a 612 bp ORF (jadR*) downstream of the dideoxysugar biosynthesis genes resembles many TetR-family transcriptional regulator sequences.

  通过染色体走查，我们找到了紧靠 jadN 下游的另外八个基因，即委内瑞拉链霉菌 ISP5230 的 jad 簇中的 jadX、O、P、Q、S、T、U 和 V。这些基因被克隆到大肠杆菌中，并通过插入带有驱动下游基因转录的启动子的阿普霉素抗性盒而失活，然后通过属间连接转入委内瑞拉链霉菌。通过高效液相色谱和核磁共振对插入失活的委内瑞拉链霉菌突变体培养物积累的中间产物进行分析表明，jadO、P、Q、S、T、U 和 V 介导了贾多霉素 B 的双脱氧糖分子的形成及其与苷元的连接。根据这些结果以及与其他物种中产生脱氧糖衍生物的基因序列相似性，提出了一种生物合成途径，其中 jadQ 产物（1-磷酸葡萄糖核苷酸转移酶）将葡萄糖活化为其核苷酸二磷酸（NDP）衍生物，jadT 产物（4,6-脱氢酶）将其转化为 NDP-4-酮-6-脱氧-D-葡萄糖。分别由 jadO 和 jadP 编码的 NDP-2,3-己糖脱氢酶和氧化还原酶催化随后的反应，生成 NDP-2,6-二脱氧-D-苏-4-己糖。jadU 的产物（NDP-4-keto-2,6-dideoxy-5-epimerase）将这一中间产物转化为 L-赤式，而 jadV 的产物（NDP-4-keto-2,6-dideoxy-6-hexose-4-ketoreductase）则还原 NDP-4-hexulose 的酮基，从而在 jadomycin B 中生成活化形式的 L-二甲氧基糖分子。最后，由 jadS 编码的糖基转移酶将活化的糖转移到金刚霉素苷元中。jadX 的功能尚不清楚；该基因对金刚霉素 B 的生物合成并不重要，但它的存在可确保苷元完全转化为苷。双脱氧糖生物合成基因下游 612 bp ORF（jadR*）的氨基酸序列推导结果与许多 TetR 家族转录调节器序列相似。
• Deoxysugars in glycopeptide antibiotics: Enzymatic synthesis of TDP- <scp>l</scp> -epivancosamine in chloroeremomycin biosynthesis
  作者：Huawei Chen、Michael G. Thomas、Brian K. Hubbard、Heather C. Losey、Christopher T. Walsh、Michael D. Burkart

  DOI：10.1073/pnas.210395097

  日期：2000.10.24

  TDP-4-keto-6-deoxy-d-glucose. This process involves C-2 deoxygenation, C-3 amination and methylation, C-5 epimerization, and C-4 ketoreduction. Intermediates and the final product of this pathway have been identified by mass spectrometry and NMR. The pathway established here represents the complete in vitro reconstitution of an unusual sugar for an important class of antibiotics and sets the groundwork for future

  2,3,6-三脱氧糖 l-表万古胺是添加到氯雷霉素（糖肽抗生素万古霉素家族成员）糖苷配基支架上的末端糖。来自氯雷霉素生物合成簇的五种蛋白质（ORF14、ORF23 至 ORF26）已在大肠杆菌中异源表达，并纯化至接近均质，并且每种蛋白质均已进行酶活性表征。这五种酶重建了从 TDP-4-酮-6-脱氧-d-葡萄糖完全生物合成 TDP-l-表万古胺。该过程涉及C-2脱氧、C-3氨基化和甲基化、C-5差向异构化和C-4酮还原。该途径的中间体和最终产物已通过质谱和核磁共振鉴定。这里建立的途径代表了一类重要抗生素的不寻常糖的完整体外重构，并为未来新生物活性化合物的组合生物合成奠定了基础。
• The mtmVUC genes of the mithramycin gene cluster in Streptomycesargillaceus are involved in the biosynthesis of the sugar moieties
  作者：A. González、L. L. Remsing、F. Lombó、M. J. Fernández、L. Prado、A. F. Braña、E. Künzel、J. Rohr、C. Méndez、J A. Salas

  DOI：10.1007/s004380000372

  日期：2001.2

  Mithramycin is a glycosylated aromatic polyketide produced by Streptomyces argillaceus, and is used as an antitumor drug. Three genes (mtmV, mtmU and mtmC) from the mithramycin gene cluster have been cloned, and characterized by DNA sequencing and by analysis of the products that accumulate in nonproducing mutants, which were generated by insertional inactivation of these genes. The mtmV gene codes for a 2,3-dehydratase that catalyzes early and common steps in the biosynthesis of the three sugars found in mithramycin (D-olivose, D-oliose and D-mycarose); its inactivation caused the accumulation of the nonglycosylated intermediate premithramycinone. The mtmU gene codes for a 4-ketoreductase involved in D-oliose biosynthesis, and its inactivation resulted in the accumulation of premithramycinone and premithramycin Al, the first glycosylated intermediate which contains a D-olivose unit. The third gene, mtmC, is involved in D-mycarose biosynthesis and codes for a C-methyltransferase. Two mutants with lesions in the mtmC gene accumulated mithramycin intermediates lacking the D-mycarose moiety but containing D-olivose units attached to C-12a in which the 4-keto group is unreduced. This suggests that mtmC could code for a second enzyme activity, probably a D-olivose 4-ketoreductase, and that the glycosyltransferase responsible for the incorporation of D-olivose (MtmGIV) shows some degree of flexibility with respect to its sugar co-substrate, since the 4-keto-analog is also transferred. A pathway is proposed for the biosynthesis of the three sugar moieties in mithramycin.