(3R,4R)-3,4-二羟基-1,5-环己二烯-1-羧酸 | 108646-25-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (3R,4R)-3,4-二羟基-1,5-环己二烯-1-羧酸
• 中文别名: 1H-咪唑-1-乙醇，4,5-二氢-，2-C15-17-未饱和。烷基衍生物。
• 英文名称: (3R,4R)-3,4-dihydroxycyclohexa-1,5-diene carboxylic acid
• 英文别名: trans-3,4-dihydroxycyclohexa-1,5-diene-1-carboxylic acid；(4R,5R)-4,5-dihydroxycyclohexa-1,5-dienecarboxylic acid；trans-3,4-Dihydroxy-3,4-dihydrobenzoesaeure；3,4-Dihydro-3,4-dihydroxybenzoesaeure；(3R,4R)-3,4-Dihydroxycyclohexa-1,5-diene-1-carboxylic acid
• CAS: 108646-25-9
• 化学式: C₇H₈O₄
• 分子量: 156.138
• InChiKey: HEZMWWAKWCSUCB-PHDIDXHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2918199090

反应信息

• 作为反应物：
  描述：

  (3R,4R)-3,4-二羟基-1,5-环己二烯-1-羧酸 在 Hyg₅ from Streptomyces hygroscopicus chorismatases 作用下， 反应 20.0h， 生成 间羟基苯甲酸
  参考文献：
  名称：

  Chorismatase Mechanisms Reveal Fundamentally Different Types of Reaction in a Single Conserved Protein Fold

  摘要：

  Chorismatases are a class of chorismate-converting enzymes involved in the biosynthetic pathways of different natural products, many of them with interesting pharmaceutical characteristics. So far, three subfamilies of chorismatases are described that convert chorismate into different (dihydro-)benzoate derivatives (CH-FkbO, CH-Hyg5, and CH-XanB2). Until now, the detailed enzyme mechanism and the molecular basis for the different reaction products were unknown. Here we show that the CH-FkbO and CH-Hyg5 subfamilies share the same protein fold, but employ fundamentally different reaction mechanisms. While the FkbO reaction is a typical hydrolysis, the Hyg5 reaction proceeds intramolecularly, most likely via an arene oxide intermediate. Two nonconserved active site residues were identified that are responsible for the different reaction mechanisms in CH-FkbO and CH-Hyg5. Further, we propose an additional amino acid residue to be responsible for the discrimination of the CH-XanB2 subfamily, which catalyzes the formation of two different hydroxybenzoate regioisomers, likely in a single active site. A multiple sequence alignment shows that these three crucial amino acid positions are located in conserved motifs and can therefore be used to assign unknown chorismatases to the corresponding subfamily.

  DOI：

  10.1021/jacs.5b05559
• 作为产物：
  描述：

  分支酸 在 FkbO from Streptomyces hygroscopicus subsp. ascomyceticus chorismatases 、 重氧水 作用下， 以 aq. buffer 为溶剂， 反应 2.0h， 生成 2-¹⁸O-pyruvic acid 、 (3R,4R)-3,4-二羟基-1,5-环己二烯-1-羧酸
  参考文献：
  名称：

  Chorismatase Mechanisms Reveal Fundamentally Different Types of Reaction in a Single Conserved Protein Fold

  摘要：

  Chorismatases are a class of chorismate-converting enzymes involved in the biosynthetic pathways of different natural products, many of them with interesting pharmaceutical characteristics. So far, three subfamilies of chorismatases are described that convert chorismate into different (dihydro-)benzoate derivatives (CH-FkbO, CH-Hyg5, and CH-XanB2). Until now, the detailed enzyme mechanism and the molecular basis for the different reaction products were unknown. Here we show that the CH-FkbO and CH-Hyg5 subfamilies share the same protein fold, but employ fundamentally different reaction mechanisms. While the FkbO reaction is a typical hydrolysis, the Hyg5 reaction proceeds intramolecularly, most likely via an arene oxide intermediate. Two nonconserved active site residues were identified that are responsible for the different reaction mechanisms in CH-FkbO and CH-Hyg5. Further, we propose an additional amino acid residue to be responsible for the discrimination of the CH-XanB2 subfamily, which catalyzes the formation of two different hydroxybenzoate regioisomers, likely in a single active site. A multiple sequence alignment shows that these three crucial amino acid positions are located in conserved motifs and can therefore be used to assign unknown chorismatases to the corresponding subfamily.

  DOI：

  10.1021/jacs.5b05559

文献信息

• Diversity-Oriented Production of Metabolites Derived from Chorismate and Their Use in Organic Synthesis
  作者：Johannes Bongaerts、Simon Esser、Volker Lorbach、Lóay Al-Momani、Michael A. Müller、Dirk Franke、Christoph Grondal、Anja Kurutsch、Robert Bujnicki、Ralf Takors、Leon Raeven、Marcel Wubbolts、Roel Bovenberg、Martin Nieger、Melanie Schürmann、Natalie Trachtmann、Stefan Kozak、Georg A. Sprenger、Michael Müller

  DOI：10.1002/anie.201103261

  日期：2011.8.16

  structure of biosynthetic pathways, such as the shikimate pathway, the selective bioproduction of a set of diverse metabolites has been achieved by means of metabolic engineering (see scheme). A scale‐up for preparative purposes was performed, resulting in high product titers and yields from renewable resources.

  以生物合成为模型：基于生物合成途径（例如the草酸途径）的分支结构，通过代谢工程（参见方案）已经实现了多种多样代谢产物的选择性生物生产。进行了用于制备目的的放大生产，从而导致较高的产品效价和可再生资源的产量。
• Biosynthetic Production of 4-Amino 4-Deoxychorismate (Adc) and [3R,4R]-4-Amino-3-Hydroxycyclohexa-1,5-Diene-1-Carboxylic Acid (3,4-Cha)
  申请人：Wubbolts Marcel Gerhardus

  公开号：US20080311631A1

  公开（公告）日：2008-12-18

  The invention relates to a process for the biosynthetic production of 4-amino-4-deoxychorismate (ADC) performed fermentatively in vivo with a 4-amino-4-deoxychorismate synthase, preferably a PabAB bipartite protein (which may be a fusion protein), at an increased level of activity, thereby obtaining a broth comprising ADC and 4-amino-4-deoxyprephenate (ADP), that are recovered. The invention also relates to a further process of converting the ADP into p-aminophenylalanine. The invention, moreover relates to biosynthetic production of [3R,4R]-4-amino-3-hydroxycyclohexa-1,5-diene-1-carboxylic acid (3,4-CHA), by concerted action of such 4-amino-4-deoxychorismate synthase and of an enzyme capable of converting isochorismate into [5S,6S]-5,6 dihydroxycyclohexa-1,3-diene-1-carboxylic acid (2,3-CHD), preferably a phenazine biosynthesis protein PhzD, including recovery of 3,4-CHA. The invention also relates to expression vectors and host cells for use in any of such processes. The invention further relates to the use of 3,4-CHA as a catalytically active product, in particular as a chiral catalyst. And the invention finally relates to synthesis of oseltamivir phosphate from 3,4-CHA.

  该发明涉及一种生物合成4-氨基-4-脱氧黄嘌呤酸（ADC）的过程，通过在体内发酵使用4-氨基-4-脱氧黄嘌呤酸合成酶，优选为PabAB二分体蛋白（可为融合蛋白）在增加的活性水平下进行，从而获得包含ADC和4-氨基-4-脱氧前苯酸（ADP）的菌液，然后进行回收。该发明还涉及将ADP转化为对氨基苯丙氨酸的进一步过程。此外，该发明还涉及通过这种4-氨基-4-脱氧黄嘌呤酸合成酶和能够将异黄嘌呤酸转化为[5S，6S]-5,6-二羟基环己基-1,3-二烯-1-羧酸（2,3-CHD）的酶的协同作用，优选为苯肼生物合成蛋白PhzD，生物合成[3R,4R]-4-氨基-3-羟基环己-1,5-二烯-1-羧酸（3,4-CHA），并回收3,4-CHA。该发明还涉及用于任何这种过程的表达载体和宿主细胞。此外，该发明还涉及将3,4-CHA用作具有催化活性的产品，特别是作为手性催化剂。最后，该发明还涉及从3,4-CHA合成奥司他韦磷酸盐的方法。
• Method for the improved production and isolation of trans-dihydroxycyclohexadiene carboxylic acids and/or derivatives thereof and genetically modified organism suitable therefor
  申请人：——

  公开号：US20030224495A1

  公开（公告）日：2003-12-04

  In the production of genetically-modified, non-pathogenic organisms particularly an improved production and isolation of trans-dihydroxycyclohexadiene carboxylic acids and/or derivatives thereof, the synthesis of the transhydroxy cyclohexadiene carboxylic acids is performed in an enantiomer-pure form without detectable impurities with chorismate by cultivation of at least one genetically altered non-pathogenic organism which has an aromate embolism and has, in comparison with a corresponding, genetically not altered organism, an increased activity of the isochorismate synthase (EntC) and isochorismatase (EntB) and an activity of the 2,3 dihydroxybenzoate synthase (EntA) which is close to zero, or an increased activity of the isochorismatase (EntB) and a reduced activity of the isochorismate synthase (EntC) and an activity of the 2,3-dihydroxybenzoat-synthase (entA) of close to zero.

  在转基因非致病生物的生产过程中，特别是在改进反式二羟基环己二烯羧酸和/或其衍生物的生产和分离过程中，反式二羟基环己二烯羧酸的合成是通过培养至少一种转基因非致病生物以对映体纯的形式进行的，没有可检测到的杂质与氯氨酸、与相应的基因未发生改变的生物体相比，异胆甾醇酯合成酶（EntC）和异胆甾醇酯合成酶（EntB）的活性增加，而 2,3-二羟基苯甲酸酯合成酶（EntA）的活性接近于零；或者异胆甾醇酯合成酶（EntB）的活性增加，而异胆甾醇酯合成酶（EntC）的活性降低，2,3-二羟基苯甲酸酯合成酶（entA）的活性接近于零。
• VERFAHREN ZUR VERBESSERTEN HERSTELLUNG UND ISOLIERUNG VON TRANS-DIHYDROXY-CYCLOHEXADIEN-CARBONSÄUREN UND/ODER DEREN FOLGEPRODUKTE SOWIE EIN DAZU GEEIGNETER GENETISCH VERÄNDERTER ORGANISMUS
  申请人：Forschungszentrum Jülich

  公开号：EP1313870B1

  公开（公告）日：2005-09-21
• Chorismatase Mechanisms Reveal Fundamentally Different Types of Reaction in a Single Conserved Protein Fold
  作者：Florian Hubrich、Puneet Juneja、Michael Müller、Kay Diederichs、Wolfram Welte、Jennifer N. Andexer

  DOI：10.1021/jacs.5b05559

  日期：2015.9.2

  Chorismatases are a class of chorismate-converting enzymes involved in the biosynthetic pathways of different natural products, many of them with interesting pharmaceutical characteristics. So far, three subfamilies of chorismatases are described that convert chorismate into different (dihydro-)benzoate derivatives (CH-FkbO, CH-Hyg5, and CH-XanB2). Until now, the detailed enzyme mechanism and the molecular basis for the different reaction products were unknown. Here we show that the CH-FkbO and CH-Hyg5 subfamilies share the same protein fold, but employ fundamentally different reaction mechanisms. While the FkbO reaction is a typical hydrolysis, the Hyg5 reaction proceeds intramolecularly, most likely via an arene oxide intermediate. Two nonconserved active site residues were identified that are responsible for the different reaction mechanisms in CH-FkbO and CH-Hyg5. Further, we propose an additional amino acid residue to be responsible for the discrimination of the CH-XanB2 subfamily, which catalyzes the formation of two different hydroxybenzoate regioisomers, likely in a single active site. A multiple sequence alignment shows that these three crucial amino acid positions are located in conserved motifs and can therefore be used to assign unknown chorismatases to the corresponding subfamily.