futalosine | 210644-32-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: futalosine
• 英文别名: Futalosine；3-[3-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-oxo-1H-purin-9-yl)oxolan-2-yl]propanoyl]benzoic acid
• CAS: 210644-32-9
• 化学式: C₁₉H₁₈N₄O₇
• 分子量: 414.375
• InChiKey: VEDWXCWBMDQNCV-SCFUHWHPSA-N

物化性质

• 沸点：
  890.2±65.0 °C(Predicted)
• 密度：
  1.73±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  163
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  futalosine 在 Thermus thermophilus N-terminal (maltose binding protein)-fused futalosine hydrolase TTHA₀₅₅₆ 作用下， 反应 0.08h， 生成 dehypoxanthinylfutalosine
  参考文献：
  名称：

  Enzymatic Properties of Futalosine Hydrolase, an Enzyme Essential to a Newly Identified Menaquinone Biosynthetic Pathway

  摘要：

  在原核生物中，脑醌用于呼吸。在大肠杆菌中，甲萘醌是通过七种酶从壳聚糖中生物合成的。然而，最近我们发现了另一种途径（富他洛苷途径），这种途径在一些细菌中运行，包括嗜热链霉、幽门螺杆菌、空肠弯曲杆菌和嗜热菌。我们描述了这一途径的步骤，它在氯甲酸酯处的分支与已知途径相似，但随后的途径不同。这条新途径包括一种由肌苷和邻代苯甲酸酯分子组成的不同寻常的核苷衍生物--富塔罗索碱（futalosine），作为生物合成的中间体。本研究制备了嗜热菌的重组富塔罗索碱水解酶（TTHA0556）并将其用于功能分析，该酶参与该途径的第二步，并催化从富塔罗索碱释放次黄嘌呤的反应。重组的 TTHA0556 形成同源四聚体，只与富塔罗索碱反应；不接受其他结构相关的核苷酸和核苷。重组 TTHA0556 不需要辅助因子，最佳 pH 值和温度分别为 4.5 和 80 °C。计算得出的 Km 值为 154.0±5.3 μm，kcat 值为 1.02/s。重组 TTHA0556 对次黄嘌呤有轻微抑制作用，Ki 值为 1.1 mm。

  DOI：

  10.1271/bbb.80906
• 作为产物：
  描述：

  3-[(1-羧基乙烯基)氧基]苯甲酸 在 sodium dithionite 、 aminofutalosine deaminase 、 aminofutalosine synthase mqnE 作用下， 以 aq. buffer 为溶剂， 反应 10.0h， 生成 futalosine
  参考文献：
  名称：

  Menaquinone Biosynthesis: Formation of Aminofutalosine Requires a Unique Radical SAM Enzyme

  摘要：

  Menaquinone (MK, vitamin K-2) is a lipid-soluble molecule that participates in the bacterial electron transport chain. In mammalian cells, MK functions as an essential vitamin for the activation of various proteins involved in blood clotting and bone metabolism. Recently, a new pathway for the biosynthesis of this cofactor was discovered in Streptomyces coelicolor A3(2) in which chorismate is converted to aminofutalosine in a reaction catalyzed by MqnA and an unidentified enzyme. Here, we reconstitute the biosynthesis of aminofutalosine and demonstrate that the missing enzyme (aminofutalosine synthase, MqnE) is a radical SAM enzyme that catalyzes the addition of the adenosyl radical to the double bond of 3-[(1-carboxyvinyl)oxy]benzoic acid. This is a new reaction type in the radical SAM superfamily.

  DOI：

  10.1021/ja408594p

文献信息

• Futalosine and Its Derivatives, New Nucleoside Analogs.
  作者：Nobuo HOSOKAWA、Hiroshi NAGANAWA、Takako KASAHARA、Seiko HATTORI、Masa HAMADA、Tomio TAKEUCHI、Shinobu YAMAMOTO、Kayoko S. TSUCHIYA、Makoto HORI

  DOI：10.1248/cpb.47.1032

  日期：——

  Futalosine, a new nucleoside analog, was isolated from a fermentation broth of Streptomyces sp. MK359-NF1. Some chemical derivatives of futalosine were prepared. 6-O-Methylfutalosine methylester inhibited growth of HeLa-S3 cells in vitro (IC50 = 19.5 micrograms/ml) in contrast to the weak activity of futalosine. 6-O-Methylfutalosine methylester at concentrations higher than 10 micrograms/ml inhibited

  从链霉菌属菌的发酵液中分离出一种新的核苷类似物富他洛星。MK359-NF1。制备了一些他他洛辛的化学衍生物。与氟他洛辛的活性较弱相反，6-O-甲基富他糖甲酯在体外可抑制HeLa-S3细胞的生长（IC50 = 19.5微克/毫升）。浓度高于10微克/毫升的6-O-甲基富他糖甲酯抑制3H-TdR和3H-UR的掺入，但不能抑制3H-Leu掺入HeLa-S3细胞的酸溶级分中。
• An efficient synthesis of futalosine
  作者：Xu Li、Martin E. Tanner

  DOI：10.1016/j.tetlet.2010.10.010

  日期：2010.12

  Futalosine is a naturally occurring nucleoside comprised of an inosine core with a 3-carboxyphenyl methylene ketone functionality replacing the C-5' hydroxyl. Recent studies have shown that it is a key intermediate in an alternative biosynthetic pathway that generates menaquinone in a variety of bacterial species. Here we report the first synthesis of futalosine in seven steps from inosine in an overall 17% yield. This work will enable further studies on menaquinone biosynthesis in pathogenic bacteria. (C) 2010 Elsevier Ltd. All rights reserved.
• Deamination of 6-Aminodeoxyfutalosine in Menaquinone Biosynthesis by Distantly Related Enzymes
  作者：Alissa M. Goble、Rafael Toro、Xu Li、Argentina Ornelas、Hao Fan、Subramaniam Eswaramoorthy、Yury Patskovsky、Brandan Hillerich、Ron Seidel、Andrej Sali、Brian K. Shoichet、Steven C. Almo、Subramanyam Swaminathan、Martin E. Tanner、Frank M. Raushel

  DOI：10.1021/bi400750a

  日期：2013.9.17

  Proteins of unknown function belonging to cog1816 and cog0402 were characterized. Sav2595 from Steptomyces avermitilis MA-4680, Ace10264 from Acidothermus cellulolyticus 11B, Nis0429 from Nitratiruptor sp. SB155-2 and Dr0824 from Deinococcus radiodurans R1 were cloned, purified, and their substrate profiles determined. These enzymes were previously incorrectly annotated as adenosine deaminases or chlorohydrolases. It was shown here that these enzymes actually deaminate 6-aminodeoxyfutalosine. The deamination of 6-aminodeoxyfutalosine is part of an alternative menaquinone biosynthetic pathway that involves the formation of futalosine. 6-Aminodeoxyfutalosine is deaminated by these enzymes with catalytic efficiencies greater than 106 M-1 s(-1), Km values of 0.9-6.0 mu M, and k(cat) values of 1.2-8.6 Adenosine, 2'-deoxyadenosine, thiomethyladenosine, and S-adenosylhomocysteine are deaminated at least an order of magnitude slower than 6-aminodeoxyfutalosine. The crystal structure of Nis0429 was determined and the substrate, 6-aminodeoxyfutalosine, was positioned in the active site on the basis of the presence of adventitiously bound benzoic acid. In this model, Ser-145 interacts with the carboxylate moiety of the substrate. The structure of.Dr0824 was also determined, but a collapsed active site pocket prevented docking of substrates. A computational model of Sav2595 was built on the basis of the crystal structure of adenosine deaminase and substrates were docked. The model predicted a conserved arginine after beta-strand 1 to be partially responsible for the substrate specificity of Sav2595.
• Menaquinone Biosynthesis: Formation of Aminofutalosine Requires a Unique Radical SAM Enzyme
  作者：Nilkamal Mahanta、Dmytro Fedoseyenko、Tohru Dairi、Tadhg P. Begley

  DOI：10.1021/ja408594p

  日期：2013.10.16

  Menaquinone (MK, vitamin K-2) is a lipid-soluble molecule that participates in the bacterial electron transport chain. In mammalian cells, MK functions as an essential vitamin for the activation of various proteins involved in blood clotting and bone metabolism. Recently, a new pathway for the biosynthesis of this cofactor was discovered in Streptomyces coelicolor A3(2) in which chorismate is converted to aminofutalosine in a reaction catalyzed by MqnA and an unidentified enzyme. Here, we reconstitute the biosynthesis of aminofutalosine and demonstrate that the missing enzyme (aminofutalosine synthase, MqnE) is a radical SAM enzyme that catalyzes the addition of the adenosyl radical to the double bond of 3-[(1-carboxyvinyl)oxy]benzoic acid. This is a new reaction type in the radical SAM superfamily.
• Enzymatic Properties of Futalosine Hydrolase, an Enzyme Essential to a Newly Identified Menaquinone Biosynthetic Pathway
  作者：Tomoshige HIRATSUKA、Nobuya ITOH、Haruo SETO、Tohru DAIRI

  DOI：10.1271/bbb.80906

  日期：2009.5.23

  In prokaryotes, menaquinone is used for respiration. In Escherichia coli, menaquinone is biosynthesized from chorismate by seven enzymes. However, very recently, we identified an alternative pathway (the futalosine pathway), which operates in some bacteria, including Streptomyces coelicolor, Helicobacter pylori, Campylobacter jejuni, and Thermus thermophilus. We describe the steps of this pathway, which branches at chorismate in a manner similar to the known pathway, but then follows a different route. This new pathway includes futalosine, an unusual nucleoside derivative consisting of inosine and o-substituted benzoate moieties, as a biosynthetic intermediate. In this study, a recombinant futalosine hydrolase (TTHA0556) of T. thermophilus, which participates in the second step of the pathway and catalyzes the reaction releasing hypoxanthine from futalosine, was prepared and used in functional analyses. Recombinant TTHA0556 formed a homotetramer and reacted only with futalosine; other structurally related nucleotides and nucleosides were not accepted. Recombinant TTHA0556 required no cofactors, and the optimum pH and temperature were 4.5 and 80 °C. The Km value was calculated to be 154.0±5.3 μm and the kcat value was 1.02/s. Recombinant TTHA0556 was slightly inhibited by hypoxanthine, with a Ki value of 1.1 mm.

  在原核生物中，脑醌用于呼吸。在大肠杆菌中，甲萘醌是通过七种酶从壳聚糖中生物合成的。然而，最近我们发现了另一种途径（富他洛苷途径），这种途径在一些细菌中运行，包括嗜热链霉、幽门螺杆菌、空肠弯曲杆菌和嗜热菌。我们描述了这一途径的步骤，它在氯甲酸酯处的分支与已知途径相似，但随后的途径不同。这条新途径包括一种由肌苷和邻代苯甲酸酯分子组成的不同寻常的核苷衍生物--富塔罗索碱（futalosine），作为生物合成的中间体。本研究制备了嗜热菌的重组富塔罗索碱水解酶（TTHA0556）并将其用于功能分析，该酶参与该途径的第二步，并催化从富塔罗索碱释放次黄嘌呤的反应。重组的 TTHA0556 形成同源四聚体，只与富塔罗索碱反应；不接受其他结构相关的核苷酸和核苷。重组 TTHA0556 不需要辅助因子，最佳 pH 值和温度分别为 4.5 和 80 °C。计算得出的 Km 值为 154.0±5.3 μm，kcat 值为 1.02/s。重组 TTHA0556 对次黄嘌呤有轻微抑制作用，Ki 值为 1.1 mm。