4-hydroxy-2-ketooctanoic acid | 781664-59-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 4-hydroxy-2-ketooctanoic acid
• 英文别名: 4-Hydroxy-2-oxooctanoic acid；4-hydroxy-2-oxooctanoic acid
• CAS: 781664-59-3
• 化学式: C₈H₁₄O₄
• 分子量: 174.197
• InChiKey: QDXJQNIRIVKJCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-hydroxy-2-ketooctanoic acid 在 盐酸 作用下， 生成 5-butyloxolane-2,3-dione
  参考文献：
  名称：

  Comparison of Two Metal-Dependent Pyruvate Aldolases Related by Convergent Evolution: Substrate Specificity, Kinetic Mechanism, and Substrate Channeling

  摘要：

  HpaI and BphI are two pyruvate class II aldolases found in aromatic meta-cleavage degradation pathways that catalyze similar reactions but are not related in sequence. Steady-state kinetic analysis of the aldol addition reactions and product inhibition assays showed that HpaI exhibits a rapid equilibrium random order mechanism while BphI exhibits a compulsory order mechanism, with pyruvate binding first. Both aldolases are able to utilize aldehyde acceptors two to five carbons in length; however, HpaI showed broader specificity and had a preference for aldehydes containing longer linear alkyl chains or C2-OH substitutions. Both enzymes were able to bind 2-keto acids larger than pyruvate, but only HpaI was able to utilize both pyruvate and 2-ketobutanoate as carbonyl donors in the aldol addition reaction. HpaI lacks stereospecific control producing racemic mixtures of 4-hydroxy-2-oxopentanoate (HOPA) from pyruvate and acetaldehyde while BphI synthesizes only (4S)-HOPA. BphI is also able to utilize acetaldehyde produced by the reduction of acetyl-CoA catalyzed by the associated aldehyde dehydrogenase, BphJ. This aldehyde was directly channeled from the dehydrogenase to the aldolase active sites, with an efficiency of 84%. Furthermore, the BphJ reductive deacylation reaction increased 4-fold when BphI was catalyzing the aldol addition reaction. Therefore, the BphI-BphJ enzyme complex exhibits unique bidirectionality in substrate channeling and allosteric activation.

  DOI：

  10.1021/bi100251u
• 作为产物：
  描述：

  正戊醛 、 piruvate 在 4-hydroxy-2-ketoheptane-1,7-dioate aldolase from Acinetobacter baumannii 、 zinc(II) chloride 作用下， 以 aq. buffer 为溶剂， 反应 1.0h， 生成 4-hydroxy-2-ketooctanoic acid
  参考文献：
  名称：

  对来自鲍曼不动杆菌的立体特异性和热稳定性 II 类醛缩酶 HpaI 的催化和结构洞察。

  摘要：

  醛缩酶催化醛醇缩合和裂解的可逆反应，具有很强的合成手性化合物的潜力，广泛用于药物。在这里，我们研究了鲍曼不动杆菌对羟基苯乙酸酯降解途径中的一种新的 II 类金属醛缩酶，即 4-羟基-2-酮-庚烷-1,7-二酸醛缩酶 (AbHpaI)，它具有适合生物催化的各种特性，包括立体选择性/立体特异性、广泛的醛利用、热稳定性和溶剂耐受性。值得注意的是，AbHpaI 使用 Zn2+ 作为天然辅因子与此类中的其他酶不同。AbHpaI 还可以使用除 Ca2+ 之外的其他金属离子 (M2+) 辅助因子进行催化。我们发现 Zn2+ 产生最高的酶复合物热稳定性（Tm 为 87 °C）和溶剂耐受性。所有 AbHpaI•M2+ 复合物均表现出对 (4R)-2-keto-3-deoxy-D-galactonate ((4R)-KDGal) 的优先裂解超过 (4S)-2-keto-3-deoxy-D-gluconate ((4S)

  DOI：

  10.1016/j.jbc.2021.101280

文献信息

• Probing the Molecular Basis of Substrate Specificity, Stereospecificity, and Catalysis in the Class II Pyruvate Aldolase, BphI
  作者：Perrin Baker、Jason Carere、Stephen Y. K. Seah

  DOI：10.1021/bi101947g

  日期：2011.5.3

  40-fold preference for propionaldehyde over acetaldehyde. The specificity constant of the L89A variant in the aldol addition reaction using pentaldehyde is increased ∼50-fold, making it more catalytically efficient for pentaldehyde utilization compared to the wild-type utilization of the natural substrate, acetaldehyde. Replacement of Tyr-290 with phenylalanine or serine resulted in a loss of stereochemical

  BphI是一种在多氯联苯（PCBs）降解途径中发现的丙酮酸特异性II类醛缩酶，可催化（4 S）-羟基-2-氧代酸的可逆C-C键裂解，形成丙酮酸和醛。突变引入了bph我探讨了活性位点残基对底物识别和催化的贡献。与对乙醛和丙醛具有相似特异性的野生型酶相反，L87A变体对丙醛的偏好性是乙醛的40倍。在使用戊醛的醛醇缩合加成反应中，L89A变体的特异性常数增加了约50倍，与天然底物乙醛的野生型利用相比，它对戊醛的利用具有更高的催化效率。用苯丙氨酸或丝氨酸替代Tyr-290会导致失去立体化学控制，因为这些变体能够利用具有R和S的底物在C4处的构型具有相似的动力学参数。在R16A变体中无法检测到Aldol裂解和丙酮酸α-质子交换活性，这支持了Arg-16在稳定丙酮酸烯醇酯中间体中的作用。酶的pH依赖性与催化碱基的单个去质子化（p K a值约为7 ）相一致。在H20A和H20S变体中，pH谱显示酶活性对
• METHOD FOR PRODUCING ORGANIC COMPOUND AND CORYNEFORM BACTERIUM
  申请人：Green Earth Institute Co., Ltd.

  公开号：EP3875590A1

  公开（公告）日：2021-09-08

  A method for producing an α-keto acid includes a step of culturing a microorganism containing a gene encoding an enzyme that catalyzes an aldol reaction between pyruvic acid and a carbonyl compound in the presence of a pyruvic acid-supplying compound selected from pyruvic acid and saccharides, and a carbonyl compound selected from an aldehyde and a ketone to produce an α-keto acid.

  一种生产α-酮酸的方法包括以下步骤：培养一种微生物，该微生物含有编码一种酶的基因，该酶可在丙酮酸供应化合物（选自丙酮酸和糖类）和羰基化合物（选自醛和酮）的存在下，催化丙酮酸和羰基化合物之间的醛醇反应，从而产生α-酮酸。
• Directed evolution of a pyruvate aldolase to recognize a long chain acyl substrate
  作者：Manoj Cheriyan、Matthew J. Walters、Brian D. Kang、Laura L. Anzaldi、Eric J. Toone、Carol A. Fierke

  DOI：10.1016/j.bmc.2011.08.056

  日期：2011.11

  The use of biological catalysts for industrial scale synthetic chemistry is highly attractive, given their cost effectiveness, high specificity that obviates the need for protecting group chemistry, and the environmentally benign nature of enzymatic procedures. Here we evolve the naturally occurring 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolases from Thermatoga maritima and Escherichia coli, into enzymes that recognize a nonfunctionalized electrophilic substrate, 2-keto-4-hydroxyoctonoate (KHO). Using an in vivo selection based on pyruvate auxotrophy, mutations were identified that lower the K-M value up to 100-fold in E. coli KDPG aldolase, and that enhance the efficiency of retro-aldol cleavage of KHO by increasing the value of k(cat)/K-M up to 25-fold in T. maritima KDPG aldolase. These data indicate that numerous mutations distal from the active site contribute to enhanced 'uniform binding' of the substrates, which is the first step in the evolution of novel catalytic activity. (C) 2011 Elsevier Ltd. All rights reserved.
• Comparison of Two Metal-Dependent Pyruvate Aldolases Related by Convergent Evolution: Substrate Specificity, Kinetic Mechanism, and Substrate Channeling
  作者：Weijun Wang、Perrin Baker、Stephen Y. K. Seah

  DOI：10.1021/bi100251u

  日期：2010.5.4

  HpaI and BphI are two pyruvate class II aldolases found in aromatic meta-cleavage degradation pathways that catalyze similar reactions but are not related in sequence. Steady-state kinetic analysis of the aldol addition reactions and product inhibition assays showed that HpaI exhibits a rapid equilibrium random order mechanism while BphI exhibits a compulsory order mechanism, with pyruvate binding first. Both aldolases are able to utilize aldehyde acceptors two to five carbons in length; however, HpaI showed broader specificity and had a preference for aldehydes containing longer linear alkyl chains or C2-OH substitutions. Both enzymes were able to bind 2-keto acids larger than pyruvate, but only HpaI was able to utilize both pyruvate and 2-ketobutanoate as carbonyl donors in the aldol addition reaction. HpaI lacks stereospecific control producing racemic mixtures of 4-hydroxy-2-oxopentanoate (HOPA) from pyruvate and acetaldehyde while BphI synthesizes only (4S)-HOPA. BphI is also able to utilize acetaldehyde produced by the reduction of acetyl-CoA catalyzed by the associated aldehyde dehydrogenase, BphJ. This aldehyde was directly channeled from the dehydrogenase to the aldolase active sites, with an efficiency of 84%. Furthermore, the BphJ reductive deacylation reaction increased 4-fold when BphI was catalyzing the aldol addition reaction. Therefore, the BphI-BphJ enzyme complex exhibits unique bidirectionality in substrate channeling and allosteric activation.
• Catalytic and structural insights into a stereospecific and thermostable Class II aldolase HpaI from Acinetobacter baumannii
  作者：Pratchaya Watthaisong、Asweena Binlaeh、Aritsara Jaruwat、Narin Lawan、Jirawat Tantipisit、Juthamas Jaroensuk、Litavadee Chuaboon、Jittima Phonbuppha、Ruchanok Tinikul、Pimchai Chaiyen、Penchit Chitnumsub、Somchart Maenpuen

  DOI：10.1016/j.jbc.2021.101280

  日期：2021.11

  Aldolases catalyze the reversible reactions of aldol condensation and cleavage and have strong potential for the synthesis of chiral compounds, widely used in pharmaceuticals. Here, we investigated a new Class II metal aldolase from the p-hydroxyphenylacetate degradation pathway in Acinetobacter baumannii, 4-hydroxy-2-keto-heptane-1,7-dioate aldolase (AbHpaI), which has various properties suitable

  醛缩酶催化醛醇缩合和裂解的可逆反应，具有很强的合成手性化合物的潜力，广泛用于药物。在这里，我们研究了鲍曼不动杆菌对羟基苯乙酸酯降解途径中的一种新的 II 类金属醛缩酶，即 4-羟基-2-酮-庚烷-1,7-二酸醛缩酶 (AbHpaI)，它具有适合生物催化的各种特性，包括立体选择性/立体特异性、广泛的醛利用、热稳定性和溶剂耐受性。值得注意的是，AbHpaI 使用 Zn2+ 作为天然辅因子与此类中的其他酶不同。AbHpaI 还可以使用除 Ca2+ 之外的其他金属离子 (M2+) 辅助因子进行催化。我们发现 Zn2+ 产生最高的酶复合物热稳定性（Tm 为 87 °C）和溶剂耐受性。所有 AbHpaI•M2+ 复合物均表现出对 (4R)-2-keto-3-deoxy-D-galactonate ((4R)-KDGal) 的优先裂解超过 (4S)-2-keto-3-deoxy-D-gluconate ((4S)