2,5-diiminio-3,4-bis(1H-indol-3-yl)hexanedioate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2,5-diiminio-3,4-bis(1H-indol-3-yl)hexanedioate
• 英文别名: 2,5-diimino-3,4-bis(1H-indol-3-yl)hexanedioic acid
• 化学式: C₂₂H₁₈N₄O₄
• 分子量: 402.4
• InChiKey: CKBGWXPNAUCVQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  154
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,5-diiminio-3,4-bis(1H-indol-3-yl)hexanedioate 生成 Chromopyrrolate 、 氢(+1)阳离子 、 铵
  参考文献：
  名称：

  Enzymatic Generation of the Chromopyrrolic Acid Scaffold of Rebeccamycin by the Tandem Action of RebO and RebD

  摘要：

  During the biosynthesis of the fused six-ring indolocarbazole scaffolds of rebeccamycin and staurosporine, two molecules of L-tryptophan are processed to a pyrrole-containing five-ring intermediate known as chromopyrrolic acid. We report here the heterologous expression of RebO and RebD from the rebeccamycin biosynthetic pathway in Escherichia coli, and tandem action of these two enzymes to construct the dicarboxypyrrole ring of chromopyrrolic acid. Chromopyrrolic acid is oxidized by six electrons compared to the starting pair Of L-tryptophan molecules. RebO is an L-tryptophan oxidase flavoprotein and RebD a heme protein dimer with both catalase and chromopyrrolic acid synthase activity. Both enzymes require dioxygen as a cosubstrate. RebD on its own is incompetent with L-tryptophan but will convert the imine of indole-3-pyruvate to chromopyrrolic acid. It displays a substrate preference for two molecules of indole-3-pyruvic acid imine, necessitating a net two-electron oxidation to give chromopyrrolic acid.

  DOI：

  10.1021/bi051706e
• 作为产物：
  描述：

  2-imino-3-(1H-indol-3-yl)propanoic acid 、 双氧水 生成 水 、 2,5-diiminio-3,4-bis(1H-indol-3-yl)hexanedioate
  参考文献：
  名称：

  Enzymatic Generation of the Chromopyrrolic Acid Scaffold of Rebeccamycin by the Tandem Action of RebO and RebD

  摘要：

  During the biosynthesis of the fused six-ring indolocarbazole scaffolds of rebeccamycin and staurosporine, two molecules of L-tryptophan are processed to a pyrrole-containing five-ring intermediate known as chromopyrrolic acid. We report here the heterologous expression of RebO and RebD from the rebeccamycin biosynthetic pathway in Escherichia coli, and tandem action of these two enzymes to construct the dicarboxypyrrole ring of chromopyrrolic acid. Chromopyrrolic acid is oxidized by six electrons compared to the starting pair Of L-tryptophan molecules. RebO is an L-tryptophan oxidase flavoprotein and RebD a heme protein dimer with both catalase and chromopyrrolic acid synthase activity. Both enzymes require dioxygen as a cosubstrate. RebD on its own is incompetent with L-tryptophan but will convert the imine of indole-3-pyruvate to chromopyrrolic acid. It displays a substrate preference for two molecules of indole-3-pyruvic acid imine, necessitating a net two-electron oxidation to give chromopyrrolic acid.

  DOI：

  10.1021/bi051706e

文献信息

• Crystal Structure of VioE, a Key Player in the Construction of the Molecular Skeleton of Violacein
  作者：Satoshi Hirano、Shumpei Asamizu、Hiroyasu Onaka、Yoshitsugu Shiro、Shingo Nagano

  DOI：10.1074/jbc.m708109200

  日期：2008.3

  is spontaneously converted to chromopyrrolic acid for indolocarbazole biosynthesis, whereas VioE transforms compound X into protodeoxyviolaceinic acid, which is further modified by other enzymes to produce violacein. Thus, VioE plays a key role in the construction of the molecular skeleton of violacein. Here, we present the crystal structure of VioE, which consists of two subunits, each of which forms

  紫罗兰素和吲哚并咔唑是天然存在的双吲哚产品，具有多种生物活性，包括抗肿瘤活性。尽管这些化合物具有明显不同的分子骨架，但它们的生物合成途径共享相同的中间体“化合物X”，该化合物是从L-色氨酸通过吲哚-3-丙酮酸亚胺产生的。化合物X是短寿命的中间体，可自发转化为吲哚并咔唑生物合成的色吡咯酸，而VioE则将化合物X转化为原脱氧紫胶酸，其被其他酶进一步修饰以生成紫胶素。因此，VioE在紫胶素分子骨架的构建中起着关键作用。在这里，我们介绍了VioE的晶体结构，它由两个亚基组成，每个亚基形成类似于棒球手套的结构。每个子单元在结构凹面的中心都有一个带正电的袋。对表面囊和其他表面残留物的诱变分析表明，表面囊起着活性位点的作用。我们还解决了作为VioE-底物复合物类似物的VioE和苯基丙酮酸复合物的晶体结构。与VioE和IPA亚胺二聚体对接的模拟（建议是化合物X）与突变分析和VioE-苯基丙酮酸复合物结构的
• Evidence for catalytic intermediates involved in generating the chromopyrrolic acid scaffold of rebeccamycin by RebO and RebD
  作者：Tatyana Spolitak、David P. Ballou

  DOI：10.1016/j.abb.2015.03.020

  日期：2015.5

  We provide the first experimental evidence for intermediates being involved in catalysis by RebD in generating the chromopyrrolic acid (CPA) scaffold of rebeccamycin. In the presence of its substrates (indole pyruvate imine - IPAI - and H2O2 both produced by the flavoprotein oxidase RebO that oxidizes tryptophan), RebD reacts as a peroxidase forming two IPAI radicals that recombine as a C-C bond in the CPA. When catalase is included to remove H2O2, CPA can still be formed because the IPAI rapidly reduces RebD, which reacts with O-2, utilizing oxidase-peroxidase chemistry to produce CPA. Reduced RebD can also react with H2O2 forming Cpd II directly, which can oxidize IPAI. Stopped-flow spectrophotometric studies demonstrated that during the reaction of RebO and RebD with Trp and oxygen, a species with a red-shifted Soret band at 424.5 nm appeared. This species can react with either guaiacol or ABTS to form ferric RebD, suggesting that it is Cpd II of RebD involved in the formation of CPA. In summary, the studies reveal new and unusual aspects peroxidase and peroxygenase chemistry used by RebD in catalyzing carbon-carbon oxidative coupling reactions that are involved in biosynthesis of indolocarbazoles. (C) 2015 Elsevier Inc. All rights reserved.
• In Vitro Biosynthesis of Violacein from <scp>l</scp>-Tryptophan by the Enzymes VioA−E from <i>Chromobacterium violaceum</i>
  作者：Carl J. Balibar、Christopher T. Walsh

  DOI：10.1021/bi061998z

  日期：2006.12.1

  The purple chromobacterial pigment violacein arises by enzymatic oxidation and coupling of two molecules of L-tryptophan to give a rearranged pyrrolidone-containing scaffold in the final pigment. We have purified five contiguously encoded proteins VioA-E after expression in Escherichia coli and demonstrate the full 14-electron oxidation pathway to yield the final chromophore. The flavoenzyme VioA and the heme protein VioB work in conjunction to oxidize and dimerize L-tryptophan to a nascent product that can default to the off pathway metabolite chromopyrrolic acid. In the presence of VioE, the intermediate instead undergoes on-pathway [1,2] indole rearrangement to prodeoxyviolacein. The last two enzymes in the pathway are flavin-dependent oxygenases, VioC and VioD, that act sequentially. VioD hydroxylates one indole ring at the 5-position to yield proviolacein, and VioC then acts on the other indole ring at the 2-position to create the oxindole and complete violacein formation.