2,3-epoxy-2,3-dihydrobenzoyl-CoA

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2,3-epoxy-2,3-dihydrobenzoyl-CoA
• 英文别名: [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-[[[[(3R)-3-hydroxy-2,2-dimethyl-4-[[3-[2-(7-oxabicyclo[4.1.0]hepta-2,4-diene-2-carbonylsulfanyl)ethylamino]-3-oxopropyl]amino]-4-oxobutoxy]-oxidophosphoryl]oxy-oxidophosphoryl]oxymethyl]oxolan-3-yl] phosphate
• 化学式: C28H36N7O18P3S-4
• 分子量: 883.6
• InChiKey: LPLMOOBQLPTXLP-XOADNVFSSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -5.6
• 重原子数：
  57
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  413
• 氢给体数：
  5
• 氢受体数：
  23

反应信息

• 作为反应物：
  描述：

  2,3-epoxy-2,3-dihydrobenzoyl-CoA 、 水 生成 cis-3,4-didehydroadipoyl-CoA semialdehyde(4-) 、 草氨酸 、 氢(+1)阳离子
  参考文献：
  名称：

  通过环氧化物形成对苯甲酸盐进行辅酶 A 依赖性有氧代谢。

  摘要：

  在芳香底物的有氧代谢中，加氧酶利用分子氧羟基化并最终裂解芳香环。在常见的中间体苯甲酸酯的情况下，开环底物是儿茶酚（在细菌中）或 3,4-二羟基苯甲酸酯（原儿茶酸酯，主要在真菌中）。我们之前已经证明，许多细菌，例如这里研究的有机体 Azoarcus evansii，使用完全不同的机制。这种复杂的途径需要形成苯甲酰辅酶 A，然后是加氧酶反应和非氧化环裂解。苯甲酰-CoA 转化由含铁的苯甲酰-CoA 加氧酶 (BoxB) 与 FAD 和含有还原酶 (BoxA) 的铁硫中心共同催化，后者从 NADPH 中提供电子。在这里我们表明苯甲酰辅酶 A 加氧酶实际上不形成 2, 苯甲酰-CoA 的 3-二氢二醇，如以前所假设的，但 2,3-环氧化物。烯酰-CoA 水合酶 (BoxC) 使用两个分子的水首先水解打开 2,3-环氧苯甲酰-CoA 的环，这可以通过其互变异构的七元氧塞平环形式进行。然后将环 C2 水解为甲酸，产生

  DOI：

  10.1074/jbc.m110.124156
• 作为产物：
  描述：

  benzoyl-CoA(4-) 、 氢(+1)阳离子 、 NADPH(4-) 、 氧气 生成 2,3-epoxy-2,3-dihydrobenzoyl-CoA 、 水 、 NADP⁺
  参考文献：
  名称：

  埃文氏变形杆菌 Azoarcus evansii 中新型好氧苯甲酸盐代谢的再研究。

  摘要：

  重新研究了变形杆菌 Azoarcus evansii 中苯甲酸盐的有氧代谢。导致儿茶酚或原儿茶酸的已知途径在这种细菌中不起作用。通过 3-羟基苯甲酰辅酶 A (CoA) 和龙胆酸盐的推测降解无法得到证实。第一个承诺的步骤是通过特异性诱导的苯甲酸-CoA 连接酶（AMP 形成）将苯甲酸激活为苯甲酰-CoA。该酶被纯化并显示与在厌氧条件下催化相同反应的同工酶不同。假设的第二步涉及通过新的苯甲酰辅酶A加氧酶（可能是多组分酶系统）将苯甲酰辅酶A羟基化为迄今为止未知的产物。一种铁硫黄素蛋白（可能是该系统的一个组成部分）被纯化和表征。通过凝胶过滤测定，同二聚酶的天然分子量为 98 kDa，每 mol 天然蛋白质含有 0.72 mol 黄素腺嘌呤二核苷酸 (FAD)、10.4 至 18.4 mol 铁和 13.3 至 17.9 mol 酸不稳定硫，取决于蛋白质的测定方法。这种苯甲酸盐诱导的酶催化了苯甲酰

  DOI：

  10.1128/jb.183.6.1899-1908.2001

文献信息

• Genes Coding for a New Pathway of Aerobic Benzoate Metabolism in <i>Azoarcus evansii</i>
  作者：Johannes Gescher、Annette Zaar、Magdy Mohamed、Hermann Schägger、Georg Fuchs

  DOI：10.1128/jb.184.22.6301-6315.2002

  日期：2002.11.15

  A new pathway for aerobic benzoate oxidation has been postulated for Azoarcus evansii and for a Bacillus stearothermophilus -like strain. Benzoate is first transformed into benzoyl coenzyme A (benzoyl-CoA), which subsequently is oxidized to 3-hydroxyadipyl-CoA and then to 3-ketoadipyl-CoA; all intermediates are CoA thioesters. The genes coding for this benzoate-induced pathway were investigated in the β-proteobacterium A. evansii . They were identified on the basis of N-terminal amino acid sequences of purified benzoate metabolic enzymes and of benzoate-induced proteins identified on two-dimensional gels. Fifteen genes probably coding for the benzoate pathway were found to be clustered on the chromosome. These genes code for the following functions: a putative ATP-dependent benzoate transport system, benzoate-CoA ligase, a putative benzoyl-CoA oxygenase, a putative isomerizing enzyme, a putative ring-opening enzyme, enzymes for β-oxidation of CoA-activated intermediates, thioesterase, and lactone hydrolase, as well as completely unknown enzymes belonging to new protein families. An unusual putative regulator protein consists of a regulator protein and a shikimate kinase I-type domain. A deletion mutant with a deletion in one gene ( boxA ) was unable to grow with benzoate as the sole organic substrate, but it was able to grow with 3-hydroxybenzoate and adipate. The data support the proposed pathway, which postulates operation of a new type of ring-hydroxylating dioxygenase acting on benzoyl-CoA and nonoxygenolytic ring cleavage. A β-oxidation-like metabolism of the ring cleavage product is thought to lead to 3-ketoadipyl-CoA, which finally is cleaved into succinyl-CoA and acetyl-CoA.

  摘要 推测了一种新的有氧苯甲酸酯氧化途径，该途径适用于 偶氮弧菌 和一种 类菌株的 -类菌株。苯甲酸首先转化为苯甲酰辅酶 A（苯甲酰-CoA），然后氧化为 3-羟基己二酰-CoA，再氧化为 3-酮基己二酰-CoA；所有中间产物都是 CoA 硫代酯。对β-蛋白细菌中编码这种苯甲酸盐诱导途径的基因进行了研究。 A. evansii .根据纯化的苯甲酸盐代谢酶和在二维凝胶上鉴定的苯甲酸盐诱导蛋白的 N 端氨基酸序列，确定了这些基因。研究发现，15 个可能编码苯甲酸盐途径的基因聚集在染色体上。这些基因编码以下功能：假定的 ATP 依赖性苯甲酸运输系统、苯甲酸-CoA 连接酶、假定的苯甲酰-CoA 加氧酶、假定的异构化酶、假定的开环酶、CoA 激活中间体的 β-氧化酶、硫酯酶和内酯水解酶，以及属于新蛋白家族的完全未知的酶。一种不寻常的推定调节蛋白由调节蛋白和莽草酸激酶 I 型结构域组成。一个基因缺失的缺失突变体（如 boxA ) 无法在以苯甲酸盐为唯一有机底物的条件下生长，但却能在以 3-羟基苯甲酸盐和己二酸盐为唯一有机底物的条件下生长。这些数据支持所提出的途径，即假定一种新型环状羟化二氧 化酶作用于苯甲酰-CoA 和非氧分解环裂解。环裂解产物的β-氧化类似代谢被认为会产生 3-酮二酰-CoA，最后裂解成琥珀酰-CoA 和乙酰-CoA。
• Aerobic benzoyl-CoA catabolic pathway in<i>Azoarcus evansii</i>: studies on the non-oxygenolytic ring cleavage enzyme
  作者：Johannes Gescher、Wolfgang Eisenreich、Jürgen Wörth、Adelbert Bacher、Georg Fuchs

  DOI：10.1111/j.1365-2958.2005.04637.x

  日期：2005.6

  SummaryA novel aerobic benzoate pathway has recently been discovered in various bacteria in which benzoate is first converted to benzoyl‐CoA. The further downstream steps are associated with the gene products of the benzoate oxidation gene cluster (box) on the Azoarcus evansii chromosome. Benzoyl‐CoA is oxidized to 2,3‐dihydro‐2,3‐dihydroxybenzoyl‐CoA (benzoyl‐CoA dihydrodiol) by benzoyl‐CoA oxygenase/reductase BoxBA in the presence of molecular oxygen. This study identified the next, ring cleaving step catalysed by BoxC. The boxC gene was expressed in a recombinant Escherichia coli strain as a fusion protein with maltose binding protein (BoxCmal) and the wild type as well as the recombinant proteins were purified and studied. BoxC catalyses the reaction 2,3‐dihydro‐2,3‐dihydroxybenzoyl‐CoA + H2O → 3,4‐dehydroadipyl‐CoA semialdehyde + HCOOH. This is supported by the following results. Assays containing [ring‐13C6]benzoyl‐CoA, benzoyl‐CoA oxygenase/reductase, BoxCmal protein, NADPH and semicarbazide were analysed directly by NMR spectroscopy and mass spectrometry. The products were identified as the semicarbazone of [2,3,4,5,6‐13C5]3,4‐dehydroadipyl‐CoA semialdehyde; the missing one‐carbon unit being formate. The same reaction mixture without semicarbazide yielded a mixture of the hydrate of [2,3,4,5,6‐13C5]3,4‐dehydroadipyl‐CoA semialdehyde and [2,3,4,5,6‐13C5]4,5‐dehydroadipyl‐CoA semialdehyde. BoxC, a 122 kDa homodimeric enzyme (61 kDa subunits), is termed benzoyl‐CoA‐dihydrodiol lyase. It contains domains characteristic for enoyl‐CoA hydratases/isomerases, besides a large central domain with no significant similarity to sequences in the database. The purified protein did not require divalent metals, molecular oxygen or any cosubstrates or coenzymes for activity. The complex reaction is part of a widely distributed new principle of aerobic aromatic metabolism in which all intermediates are coenzyme A thioesters and the actual ring‐cleavage reaction does not require molecular oxygen.
• New enzymes involved in aerobic benzoate metabolism in Azoarcus evansii
  作者：Annette Zaar、Johannes Gescher、Wolfgang Eisenreich、Adelbert Bacher、Georg Fuchs

  DOI：10.1111/j.1365-2958.2004.04263.x

  日期：——

  SummaryA new principle of aerobic aromatic metabolism has been postulated, which is in contrast to the known pathways. In various bacteria the aromatic substrate benzoate is first converted to its coenzyme A (CoA) thioester, benzoyl‐CoA, which is subsequently attacked by an oxygenase, followed by a non‐oxygenolytic fission of the ring. We provide evidence for this hypothesis and show that benzoyl‐CoA conversion in the bacterium Azoarcus evansii requires NADPH, O2 and two protein components, BoxA and BoxB. BoxA is a homodimeric 46 kDa iron‐sulphur‐flavoprotein, which acts as reductase. In the absence of BoxB, BoxA catalyses the benzoyl‐CoA stimulated artificial transfer of electrons from NADPH to O2 via free FADH2 to produce H2O2. Physiologically, BoxA uses NADPH to reduce BoxB, a monomeric 55 kDa iron‐protein that acts as benzoyl‐CoA oxygenase. The product of benzoyl‐CoA oxidation was identified by NMR spectroscopy as its dihydrodiol derivative, 2,3‐dihydro‐2,3‐dihydroxybenzoyl‐CoA. This suggests that BoxBA act as a benzoyl‐CoA dioxygenase/reductase. Unexpectedly, benzoyl‐CoA transformation by BoxBA was greatly stimulated when another enoyl‐CoA hydratase/isomerase‐like protein, BoxC, was added that catalysed the further transformation of the dihydrodiol product formed from benzoyl‐CoA. The benzoyl‐CoA oxygenase system has very low similarity to known (di)oxygenase systems and is the first member of a new enzyme family.