4-hydroxy-2-oxohexanoic acid | 3545-21-9

• 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-oxohexanoic acid
• 英文别名: 4-hydroxy-2-ketohexanoic acid；HOHA；2-Oxo-4-hydroxycapronsaeure
• CAS: 3545-21-9
• 化学式: C₆H₁₀O₄
• mdl: MFCD19230517
• 分子量: 146.143
• InChiKey: ALFQPWXBAWHVDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.666
• 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-oxohexanoic acid 在 盐酸 作用下， 生成 5-ethyl-dihydro-furan-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：

  piruvate 、 丙醛 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-oxohexanoic 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
• Redesigning Aldolase Stereoselectivity by Homologous Grafting
  作者：Carolin Bisterfeld、Thomas Classen、Irene Küberl、Birgit Henßen、Alexander Metz、Holger Gohlke、Jörg Pietruszka

  DOI：10.1371/journal.pone.0156525

  日期：——

  in DERA. We identified such positions by structural analysis of the homologous aldolases 2-keto-3-deoxy-6-phosphogluconate aldolase (KDPG) and the enantiocomplementary enzyme 2-keto-3-deoxy-6-phosphogalactonate aldolase (KDPGal). Mutation of these positions led to a slightly inversed enantiopreference of both aldolases to the same extent. By transferring these sequence motifs onto DERA we achieved

  2-脱氧-d-核糖-5-磷酸醛缩酶（DERA）通过催化乙醛和某些亲电子醛之间的立体选择性CC键形成，为有机合成提供了非常理想的结构单元。催化连续的，高度对映选择性的羟醛反应的能力特别突出了DERA的潜力。然而，由于缺乏对映体互补酶，其合成用途受到限制。在这里，我们介绍了同源嫁接的概念，以确定在DERA中确定立体选择性的氨基酸位置。我们通过同源醛缩酶2-酮-3-脱氧-6-磷酸葡糖醛酸醛缩酶（KDPG）和对映体互补酶2-酮-3-脱氧-6-磷酸半乳糖醛酸醛缩酶（KDPGal）的结构分析确定了这些位置。这些位置的突变导致两种醛缩酶的对映体略有倒置。通过将这些序列基序转移到DERA上，我们实现了对映选择性的预期变化。
• Probe compound for detecting and isolating enzymes and means and methods using the same
  申请人：Helmholtz-Zentrum für Infektionsforschung GmbH

  公开号：EP2230312A1

  公开（公告）日：2010-09-22

  The present invention relates to a probe compound that can comprise any substrate or metabolite of an enzymatic reaction in addition to an indicator component, such as, for example, a fluorescence dye, or the like. Moreover, the present invention relates to means for detecting enzymes in form of an array, which comprises any number of probe compounds of the invention which each comprise a different metabolite of interconnected metabolites representing the central pathways in all forms of life. Moreover, the present invention relates to a method for detecting enzymes involving the application of cell extracts or the like to the array of the invention which leads to reproducible enzymatic reactions with the substrates. These specific enzymatic reactions trigger the indicator (e.g. a fluorescence signal) and bind the enzymes to the respective cognate substrates. Moreover, the invention relates to means for isolating enzymes in form of nanoparticles coated with the probe compound of the invention. The immobilisation of the cognate substrates or metabolites on the surface of nanoparticles by means of the probe compounds allows capturing and isolating the respective enzyme, e.g. for subsequent sequencing.

  本发明涉及一种探针化合物，它可以包括酶反应的任何底物或代谢物，此外还包括指示成分，例如荧光染料或类似物。此外，本发明还涉及以阵列形式检测酶的方法，该阵列由任意数量的本发明探针化合物组成，每种探针化合物由代表所有生命形式中中心途径的相互关联的代谢物中的不同代谢物组成。此外，本发明还涉及一种检测酶的方法，该方法涉及将细胞提取物或类似物应用于本发明的阵列，从而导致与底物发生可重复的酶反应。这些特定的酶反应会触发指示剂（如荧光信号），并将酶与各自的同源底物结合。此外，本发明还涉及以涂覆有本发明探针化合物的纳米颗粒形式分离酶的方法。通过探针化合物将同源底物或代谢物固定在纳米颗粒表面，可以捕获和分离相应的酶，例如用于后续测序。
• 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。
• A HIGH YIELD ROUTE FOR THE PRODUCTION OF COMPOUNDS FROM RENEWABLE SOURCES
  申请人：Zymochem Inc.

  公开号：EP3047030A2

  公开（公告）日：2016-07-27