hydroxymethylphosphonate | 62305-76-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: hydroxymethylphosphonate
• 英文别名: HMP；Hydroxymethylphosphonate(1-)；hydroxy(hydroxymethyl)phosphinate
• CAS: 62305-76-4
• 化学式: CH₄O₄P
• 分子量: 111.014
• InChiKey: GTTBQSNGUYHPNK-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  6
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  hydroxymethylphosphonate 、 氧气 生成 草氨酸 、 氢(+1)阳离子 、 H3PO4
  参考文献：
  名称：

  微生物利用甲基膦酸作为磷酸盐源的氧化途径。

  摘要：

  甲基膦酸是由海洋细菌合成的，是溶解的有机磷的重要组成部分。因此，甲基膦酸还可以作为缺乏这种营养的海洋细菌的无机磷酸盐（Pi）的来源。目前仅已知通过碳-磷裂解酶途径发生甲基膦酸向Pi的转化，产生副产物甲烷。在这项工作中，我们描述了Gimesia maris DSM8797中甲基膦酸分解代谢的氧化途径。尽管缺乏编码碳-磷裂解酶途径的phn操纵子，但马氏酵母仍可以使用甲基膦酸作为Pi来源。相反，该基因组包含一个编码非血红素依赖Fe（II）的加氧酶HF130PhnY *和HF130PhnZ的同源物的基因座，先前已证明可将2-氨基乙基膦酸转化为甘氨酸和Pi。GmPhnY *和GmPhnZ1在大肠杆菌中生产，并纯化用于体外表征。用一组合成的膦酸酯评估酶的底物特异性。通过31 P NMR光谱证明，GmPhnY *将甲基膦酸转化为羟甲基膦酸，然后被GmPhnZ1氧化生成甲酸和Pi。相反，2-氨基乙基膦酸不是GmPhnY

  DOI：

  10.1021/acschembio.9b00024
• 作为产物：
  描述：

  2-(13)C-HEP 在 氧气 作用下， 生成 甲酸-13C 、 hydroxymethylphosphonate
  参考文献：
  名称：

  膦丝菌素生物合成过程中不寻常的碳-碳键裂解反应

  摘要：

  含有磷碳键的天然产物已广泛用于医学和农业。一种这样的化合物，膦丝菌素三肽，含有与两个丙氨酸残基相连的罕见氨基酸膦丝菌素。合成膦丝菌素（草铵膦）是两种畅销除草剂（Basta 和 Liberty）的成分，广泛用于抗性转基因作物，包括玉米、棉花和油菜。最近的遗传和生化研究表明，在膦丝菌素三肽生物合成过程中，2-羟乙基膦酸酯 (HEP) 被转化为羟甲基膦酸酯 (HMP)。在这里，我们报告了这种前所未有的 C(sp3)–C(sp3) 键裂解反应的体外重组和酶的 X 射线晶体结构。该蛋白质是一种单核非血红素铁 (ii) 依赖性双加氧酶，可将 HEP 转化为 HMP 和甲酸。与该家族的大多数其他成员相比，HEP 的氧化消耗不需要额外的辅助因子或外源电子的输入。目前的研究扩大了由 2-His-1-羧酸单核非血红素铁家族酶催化的反应范围。

  DOI：

  10.1038/nature07972

文献信息

• Hydroperoxylation by Hydroxyethylphosphonate Dioxygenase
  作者：John T. Whitteck、Robert M. Cicchillo、Wilfred A. van der Donk

  DOI：10.1021/ja906238r

  日期：2009.11.11

  Hydroxyethylphosphonate dioxygenase (HEPD) catalyzes the O-2-dependent cleavage of the carbon-carbon bond of 2-hydroxyethylphosphonate (2-HEP) to afford hydroxymethylphosphonate (HMP) and formate without input of electrons or use of any organic cofactors. Two mechanisms have been proposed to account for this reaction. One involves initial hydroxylation of substrate to an acetal intermediate and its subsequent attack onto an Fe(IV)-oxo species. The second mechanism features initial hydroperoxylation of substrate followed by a Criegee rearrangement. To distinguish between the two mechanisms, substrate analogues were synthesized and presented to the enzyme. Hydroxymethylphosphonate was converted into phosphate and formate, and 1 -hydroxyethylphosphonate was converted to acetylphosphate, which is an inhibitor of the enzyme. These results provide strong support for a Criegee rearrangement with a phosphorus-based migrating group and require that the O-O bond of molecular oxygen is not cleaved prior to substrate activation. (2R)-Hydroxypropylphosphonate partitioned between conversion to 2-oxopropylphosphonate and hydroxymethylphosphonate, with the latter in turn converted to phosphate and formate. Collectively, these results support a mechanism that proceeds by hydroperoxylation followed by a Criegee rearrangement.
• A Common Late-Stage Intermediate in Catalysis by 2-Hydroxyethyl-phosphonate Dioxygenase and Methylphosphonate Synthase
  作者：Spencer C. Peck、Jonathan R. Chekan、Emily C. Ulrich、Satish K. Nair、Wilfred A. van der Donk

  DOI：10.1021/jacs.5b00282

  日期：2015.3.11

  2-Hydroxyethylphosphonate dioxygenase (HEPD) and methylphosphonate synthase (MPnS) are nonheme iron oxygenases that-both catalyze the carbon carbon bond cleavage of 2-hydroxyethylphosphonate but generate different products. Substrate labeling experiments led to a mechanistic hypothesis in which the fate of a common intetmediate determined product identity. We report here the generation of a bifunctional mutant of HEPD (E176H) that exhibits the activity of both HEPD and MPnS. The product distribution of the mutant is sensitive to a substrate isotope effect, consistent with an isotope-sensitive branching mechanism involving a common intermediate: The X-ray structure of the mutant was determined and suggested that the introduced histidine does not coordinate the active site metal, unlike the iron-binding glutamate it replaced.
• On the Stereochemistry of 2-Hydroxyethylphosphonate Dioxygenase
  作者：John T. Whitteck、Petra Malova、Spencer C. Peck、Robert M. Cicchillo、Friedrich Hammerschmidt、Wilfred A. van der Donk

  DOI：10.1021/ja1113326

  日期：2011.3.30

  Stereochemical investigations have shown that the conversion of 2-hydroxyethylphosphonate to hydroxymethylphosphonate by the enzyme HEPD involves removal of the pro-S hydrogen at C2 and, surprisingly, the loss of stereochemical information at C1. As a result, the mechanisms previously proposed for HEPD must be re-evaluated.
• Mechanism and Substrate Recognition of 2-Hydroxyethylphosphonate Dioxygenase
  作者：Spencer C. Peck、Heather A. Cooke、Robert M. Cicchillo、Petra Malova、Friedrich Hammerschmidt、Satish K. Nair、Wilfred A. van der Donk

  DOI：10.1021/bi200804r

  日期：2011.8.2

  HEPD belongs to the superfamily of 2-His-1-carboxylate non-heme iron-dependent dioxygenases. It converts 2-hydroxyethylphosphonate (2-HEP) to hydroxymethylphosphonate (HMP) and formate. Previously postulated mechanisms for the reaction catalyzed by HEPD cannot explain its conversion of 1-HEP to acetylphosphate. Alternative mechanisms that involve either phosphite or methylphosphonate as intermediates, which potentially explain all experimental studies induding isotope labeling experiments and use of substrate analogues, were investigated. The results of these studies reveal that these alternative mechanisms are not correct. Site-directed mutagenesis studies of Lys16,Arg90, and Tyr98 support roles of these residues in binding of 2-HEP. Mutation of Lys16 to Ala resulted in an inactive enzyme, whereas mutation of Arg90 to Ala or Tyr98 to Phe greatly decreased k(cat)/K-m,K-2-HEP. Furthermore, the latter mutants could not be saturated in O-2. These results suggest that proper binding of 2-HEP is important for O-2 activation and that the enzyme uses a compulsory binding order with 2-HEP binding before O-2. The Y98F mutant produces methylphosphonate as a minor side product providing indirect support for the proposal that the last step during catalysis involves a ferric hydroxide reacting with a methylphosphonate radical.
• An unusual carbon–carbon bond cleavage reaction during phosphinothricin biosynthesis
  作者：Robert M. Cicchillo、Houjin Zhang、Joshua A. V. Blodgett、John T. Whitteck、Gongyong Li、Satish K. Nair、Wilfred A. van der Donk、William W. Metcalf

  DOI：10.1038/nature07972

  日期：2009.6

  phosphinothricin tripeptide biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP). Here we report the in vitro reconstitution of this unprecedented C(sp3)–C(sp3) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-haem iron(ii)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members

  含有磷碳键的天然产物已广泛用于医学和农业。一种这样的化合物，膦丝菌素三肽，含有与两个丙氨酸残基相连的罕见氨基酸膦丝菌素。合成膦丝菌素（草铵膦）是两种畅销除草剂（Basta 和 Liberty）的成分，广泛用于抗性转基因作物，包括玉米、棉花和油菜。最近的遗传和生化研究表明，在膦丝菌素三肽生物合成过程中，2-羟乙基膦酸酯 (HEP) 被转化为羟甲基膦酸酯 (HMP)。在这里，我们报告了这种前所未有的 C(sp3)–C(sp3) 键裂解反应的体外重组和酶的 X 射线晶体结构。该蛋白质是一种单核非血红素铁 (ii) 依赖性双加氧酶，可将 HEP 转化为 HMP 和甲酸。与该家族的大多数其他成员相比，HEP 的氧化消耗不需要额外的辅助因子或外源电子的输入。目前的研究扩大了由 2-His-1-羧酸单核非血红素铁家族酶催化的反应范围。