dehypoxanthinylfutalosine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: dehypoxanthinylfutalosine
• 英文别名: futalosine；Dehypoxanthine futalosine；3-[3-[(2R,3S,4R)-3,4,5-trihydroxyoxolan-2-yl]propanoyl]benzoic acid
• 化学式: C₁₄H₁₆O₇
• 分子量: 296.277
• InChiKey: XWPBBHHZDYSYMS-ZXRVKKJVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dehypoxanthinylfutalosine 、 S-腺苷-L-蛋氨酸 在 sodium dithionite 、 radical S‑adenosylmethionine enzyme MqnC 作用下， 以 aq. phosphate buffer 为溶剂， 生成 (3'S,4'R)-3',4',5'-trihydroxy-8-oxospiro[6,7-dihydronaphthalene-5,2'-oxolane]-2-carboxylic acid 、 脱氧腺嘌呤核苷
  参考文献：
  名称：

  参与 Futalosine 衍生的甲基萘醌生物合成的自由基 S-腺苷甲硫氨酸酶 MqnC 的体外重组

  摘要：

  自由基S-腺苷甲硫氨酸酶 MqnC 催化脱次黄嘌呤二氢呋喃 (DHFL) 转化为甲基萘醌生物合成的五氢呋喃途径中独特的螺环化合物环状 DHFL。本研究描述了[4Fe-4S] 簇依赖性 MqnC 活性的体外重建，并确定了腺苷自由基从 DHFL 中提取氢原子的位点。

  DOI：

  10.1021/bi400498d
• 作为产物：
  描述：

  methyl m-enolpyruvylbenzoate 在 sodium dithionite 、 aminofutalosine glycosidase, MqnB 、 aminofutalosine synthase mqnE 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 13.0h， 生成 dehypoxanthinylfutalosine
  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

• 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。
• 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.
• <i>In Vitro</i> Reconstitution of the Radical <i>S</i>-Adenosylmethionine Enzyme MqnC Involved in the Biosynthesis of Futalosine-Derived Menaquinone
  作者：Lisa E. Cooper、Dmytro Fedoseyenko、Sameh H. Abdelwahed、Soong-Hyun Kim、Tohru Dairi、Tadhg P. Begley

  DOI：10.1021/bi400498d

  日期：2013.7.9

  The radical S-adenosylmethionine enzyme MqnC catalyzes conversion of dehypoxanthine futalosine (DHFL) to the unique spiro compound cyclic DHFL in the futalosine pathway for menaquinone biosynthesis. This study describes the in vitro reconstitution of [4Fe-4S] cluster-dependent MqnC activity and identifies the site of abstraction of a hydrogen atom from DHFL by the adenosyl radical.

  自由基S-腺苷甲硫氨酸酶 MqnC 催化脱次黄嘌呤二氢呋喃 (DHFL) 转化为甲基萘醌生物合成的五氢呋喃途径中独特的螺环化合物环状 DHFL。本研究描述了[4Fe-4S] 簇依赖性 MqnC 活性的体外重建，并确定了腺苷自由基从 DHFL 中提取氢原子的位点。