N5-hydroxy-D-ornithine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N5-hydroxy-D-ornithine
• 英文别名: D-N5-hydroxyornithine；D-hOrn；(2R)-2-amino-5-(hydroxyamino)pentanoic acid
• 化学式: C₅H₁₂N₂O₃
• 分子量: 148.162
• InChiKey: OZMJDTPATROLQC-SCSAIBSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.4
• 重原子数：
  10
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  95.6
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N5-hydroxy-D-ornithine 、 (R)-3-hydroxybutyryl-Coenzyme A 在 Rhizobium etli CFN₄₂ ATCC₅₁₂₅₁ VbsA acyltransferase 作用下， 生成 N5-((R)-hydroxybutyryl)-N5-hydroxy-D-ornithine
  参考文献：
  名称：

  Enzymatic Tailoring of Ornithine in the Biosynthesis of the Rhizobium Cyclic Trihydroxamate Siderophore Vicibactin

  摘要：

  To acquire iron, the N-2-fixing, symbiotic bacterium Rhizobium sp. produce the cyclic trihydroxamate siderophore vicibactin, containing a 30-membered trilactone scaffold. Herein we report the overproduction and purification of the six proteins VbsACGOLS in the bacterial host Escherichia coli and the reconstitution of the biosynthesis of vicibactin from primary metabolites. The flavoprotein VbsO acts as a pathway-initiating L-ornithine M-hydroxylase, followed by VbsA, which transfers (R)-3-hydroxybutyryl- from the CoA thioester to N-6-hydroxyornithine to yield N-6-((R)-3-hydroxybutyryl)-N-6-hydroxy-L-orinithine. VbsL is a PLP-dependent epimerase acting at C-2 of the 10 atom monomer unit. VbsS, a nonribosomal peptide synthetase freestanding module, then activates N-6-((R)-3-hydroxybutyryl)-N-6-hydroxy-D-ornithine as the AMP anhydride on the way to cyclotrimerization to the vicibactin scaffold. The last step, tris-acetylation of the C-2 amino group of desacetyl-D-vicibactin to the mature siderophore vicibactin, is catalyzed distributively by VbsC, using three molecules of acetyl-CoA.

  DOI：

  10.1021/ja9056008
• 作为产物：
  描述：

  D-鸟氨酸 在 R₂₇₉A mutant 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.08h， 生成 N5-hydroxy-D-ornithine
  参考文献：
  名称：

  Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA

  摘要：

  Siderophore A (SidA) is a flavin-dependent monooxygenase that catalyzes the NAD(P)H- and oxygen-dependent hydroxylation of ornithine in the biosynthesis of siderophores in Aspergillus fumigatus and is essential for virulence. SidA can utilize both NADPH or NADH for activity; however, the enzyme is selective for NADPH. Structural analysis shows that R279 interacts with the 2'-phosphate of NADPH. To probe the role of electrostatic interactions in coenzyme selectivity, R279 was mutated to both an alanine and a glutamate. The mutant proteins were active but highly uncoupled, oxidizing NADPH and producing hydrogen peroxide instead of hydroxylated ornithine. For wtSidA, the catalytic efficiency was 6-fold higher with NADPH as compared to NADH. For the R279A mutant the catalytic efficiency was the same with both coenyzmes, while for the R279E mutant the catalytic efficiency was 5-fold higher with NADH. The effects are mainly due to an increase in the K-D values, as no major changes on the k(cat) or flavin reduction values were observed. Thus, the absence of a positive charge leads to no coenzyme selectivity while introduction of a negative charge leads to preference for NADH. Flavin fluorescence studies suggest altered interaction between the flavin and NADP(+) in the mutant enzymes. The effects are caused by different binding modes of the coenzyme upon removal of the positive charge at position 279, as no major conformational changes were observed in the structure for R279A. The results indicate that the positive charge at position 279 is critical for tight binding of NADPH and efficient hydroxylation. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbapap.2014.02.005

文献信息

• Synthesis of<i>N</i>^δ-Hydroxyornithine
  作者：Yoshikazu Isowa、Toshiyuki Takashima、Muneki Ohmori、Hideaki Kurita、Masanari Sato、Kaoru Mori

  DOI：10.1246/bcsj.45.1461

  日期：1972.5

  Nδ-Tosyl-Nδ-benzyloxy-Dl-ornithine was synthesized starting from γ-(N-tosyl-N-benzyloxy)-aminopropyl bromide and diethyl acetamidomalonate and resolved enzymatically to give the l- and d-isomers. Removal of one or both of protecting groups gave Nδ-benzyloxyornithine or Nδ-hydroxyornithine. The reduction product of Nδ-hydroxy-l-ornithine was identical with authentic l-ornithine.

  Nδ-甲苯磺酰基-Nδ-苯甲氧基-D1-鸟氨酸以γ-(N-甲苯磺酰基-N-苯甲氧基)-氨基丙基溴和乙酰氨基丙二酸二乙酯为原料合成，并通过酶法拆分得到l-和d-异构体。除去一个或两个保护基团得到Nδ-苄氧基鸟氨酸或Nδ-羟基鸟氨酸。 Nδ-羟基-L-鸟氨酸的还原产物与正品L-鸟氨酸相同。
• Acylation of<i>N</i>^δ-Benzyloxyornithine
  作者：Yoshikazu Isowa、Toshiyuki Takashima、Muneki Ohmori、Hideaki Kurita、Masanari Sato、Kaoru Mori

  DOI：10.1246/bcsj.45.1464

  日期：1972.5

  the other hand, acetylation or alkoxycarbonylation of Nδ-benzyloxyornithine(I) proceeded through Nα-acetylation, followed by spontaneous cyclization to form lactams, which yielded cyclic hydroxamic acids on catalytic reduction. These hydroxamic acid and Nδ-acetyl-Nδ-hydroxyornithine were readily hydrolyzed to give Nδ-hydroxyornithine.

  Nδ-苄氧基鸟氨酸单氢溴酸盐 (I·HBr) 与乙酸酐乙酰化得到 Nδ-乙酰化产物，通过催化还原生成 Nδ-乙酰基-Nδ-羟基鸟氨酸。另一方面，Nδ-苄氧基鸟氨酸(I)的乙酰化或烷氧基羰基化通过Nα-乙酰化进行，然后自发环化形成内酰胺，催化还原生成环状异羟肟酸。这些异羟肟酸和Nδ-乙酰基-Nδ-羟基鸟氨酸很容易水解得到Nδ-羟基鸟氨酸。
• Erythrochelin - a hydroxamate-type siderophore predicted from the genome of Saccharopolyspora erythraea
  作者：Lars Robbel、Thomas A. Knappe、Uwe Linne、Xiulan Xie、Mohamed A. Marahiel

  DOI：10.1111/j.1742-4658.2009.07512.x

  日期：2010.2

  siderophores encompasses a multitude of structurally diverse natural products. The genome of the erythromycin‐producing strain Saccharopolyspora erythraea contains 25 secondary metabolite gene clusters that are mostly considered to be orphan, including two that are responsible for siderophore assembly. In the present study, we report the isolation and structural elucidation of the hydroxamate‐type tetrapeptide

  非核糖体组装的铁载体类包括多种结构多样的天然产物。产生红霉素的菌株Saccharopolyspora erythraea的基因组包含25个次级代谢产物基因簇，这些簇大多被认为是孤儿，包括两个负责铁载体组装的簇。在本研究中，我们报道了异羟肟酸酯型四肽铁载体赤藓红素的分离和结构解析，这是第一种非核糖体肽合成酶衍生的红细菌天然产物。为了替代传统的活性测定指导的新型次生代谢产物的分离，我们采用了专门的radio-LC-MS方法来鉴定工业相关菌株中隐性基因簇的非核糖体肽。该方法基于转录组数据和腺苷酸化域特异性预测，并导致检测到放射性标记的鸟氨酸继承异羟肟酸酯型铁载体。改善了铁载体的生成，可以通过NMR和MSn分析以及用于确定氨基酸构型的水解产物衍生化来阐明整体结构。四肽铁载体赤藓红素的序列被确定为d-N-乙酰基-δ-N-乙酰基-δ-N-羟基鸟氨酸-d-丝氨酸-环（l-δ-N-羟基鸟氨酸-l-δ-N
• Enzymatic Tailoring of Ornithine in the Biosynthesis of the <i>Rhizobium</i> Cyclic Trihydroxamate Siderophore Vicibactin
  作者：John R. Heemstra、Christopher T. Walsh、Elizabeth S. Sattely

  DOI：10.1021/ja9056008

  日期：2009.10.28

  To acquire iron, the N-2-fixing, symbiotic bacterium Rhizobium sp. produce the cyclic trihydroxamate siderophore vicibactin, containing a 30-membered trilactone scaffold. Herein we report the overproduction and purification of the six proteins VbsACGOLS in the bacterial host Escherichia coli and the reconstitution of the biosynthesis of vicibactin from primary metabolites. The flavoprotein VbsO acts as a pathway-initiating L-ornithine M-hydroxylase, followed by VbsA, which transfers (R)-3-hydroxybutyryl- from the CoA thioester to N-6-hydroxyornithine to yield N-6-((R)-3-hydroxybutyryl)-N-6-hydroxy-L-orinithine. VbsL is a PLP-dependent epimerase acting at C-2 of the 10 atom monomer unit. VbsS, a nonribosomal peptide synthetase freestanding module, then activates N-6-((R)-3-hydroxybutyryl)-N-6-hydroxy-D-ornithine as the AMP anhydride on the way to cyclotrimerization to the vicibactin scaffold. The last step, tris-acetylation of the C-2 amino group of desacetyl-D-vicibactin to the mature siderophore vicibactin, is catalyzed distributively by VbsC, using three molecules of acetyl-CoA.
• Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA
  作者：Reeder Robinson、Stefano Franceschini、Michael Fedkenheuer、Pedro J. Rodriguez、Jacob Ellerbrock、Elvira Romero、Maria Paulina Echandi、Julia S. Martin del Campo、Pablo Sobrado

  DOI：10.1016/j.bbapap.2014.02.005

  日期：2014.4

  Siderophore A (SidA) is a flavin-dependent monooxygenase that catalyzes the NAD(P)H- and oxygen-dependent hydroxylation of ornithine in the biosynthesis of siderophores in Aspergillus fumigatus and is essential for virulence. SidA can utilize both NADPH or NADH for activity; however, the enzyme is selective for NADPH. Structural analysis shows that R279 interacts with the 2'-phosphate of NADPH. To probe the role of electrostatic interactions in coenzyme selectivity, R279 was mutated to both an alanine and a glutamate. The mutant proteins were active but highly uncoupled, oxidizing NADPH and producing hydrogen peroxide instead of hydroxylated ornithine. For wtSidA, the catalytic efficiency was 6-fold higher with NADPH as compared to NADH. For the R279A mutant the catalytic efficiency was the same with both coenyzmes, while for the R279E mutant the catalytic efficiency was 5-fold higher with NADH. The effects are mainly due to an increase in the K-D values, as no major changes on the k(cat) or flavin reduction values were observed. Thus, the absence of a positive charge leads to no coenzyme selectivity while introduction of a negative charge leads to preference for NADH. Flavin fluorescence studies suggest altered interaction between the flavin and NADP(+) in the mutant enzymes. The effects are caused by different binding modes of the coenzyme upon removal of the positive charge at position 279, as no major conformational changes were observed in the structure for R279A. The results indicate that the positive charge at position 279 is critical for tight binding of NADPH and efficient hydroxylation. (C) 2014 Elsevier B.V. All rights reserved.