4-羟基-2-氧代戊酸 | 3318-73-8

• 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
• 中文名称: 4-羟基-2-氧代戊酸
• 英文名称: 4-hydroxy-2-oxopentanoic acid
• CAS: 3318-73-8
• 化学式: C₅H₈O₄
• mdl: MFCD19228746
• 分子量: 132.116
• InChiKey: HFKQINMYQUXOCH-UHFFFAOYSA-N

物化性质

• 溶解度：
  甲醇（微溶）、水（微溶、加热、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 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-羟基-2-氧代戊酸 在 4-hydroxy 2-oxovalerate decarboxylase 作用下， 生成 3-羟基丁醛
  参考文献：
  名称：

  [EN] MICROORGANISMS FOR PRODUCING 4C-5C COMPOUNDS WITH UNSATURATION AND METHODS RELATED THERETO
  [FR] MICRO-ORGANISMES POUR LA PRODUCTION DE COMPOSÉS EN 4C-5 C AVEC UNE INSATURATION ET PROCÉDÉS ASSOCIÉS

  摘要：

  该发明提供了一种具有丁二烯、丁烯醇、2,4-戊二烯酸酯、3-丁烯-2-醇或3-丁烯-1-醇途径的非自然微生物生物体。该微生物生物体含有至少一个编码途径中酶的外源核酸。该发明还提供了一种生产丁二烯、丁烯醇、2,4-戊二烯酸酯、3-丁烯-2-醇或3-丁烯-1-醇的方法。该方法可以包括培养一种生产丁二烯、丁烯醇、2,4-戊二烯酸酯、3-丁烯-2-醇或3-丁烯-1-醇的微生物生物体，其中该微生物生物体表达至少一个编码途径酶的外源核酸，且在足够的量下，在适当的条件和足够的时间内产生丁二烯、丁烯醇、2,4-戊二烯酸酯、3-丁烯-2-醇或3-丁烯-1-醇。

  公开号：

  WO2016004334A1
• 作为产物：
  描述：

  4-methyl-2-oxobutyrolactone 在 水 、 sodium hydroxide 作用下， 生成 4-羟基-2-氧代戊酸
  参考文献：
  名称：

  Mechanism of the dehydrogenase reaction of DmpFG and analysis of inter-subunit channeling efficiency and thermodynamic parameters in the overall reaction

  摘要：

  The bifunctional, microbial enzyme DmpFG is comprised of two subunits: the aldolase, DmpG, and the dehydrogenase, DmpF. DmpFG is of interest due to its ability to channel substrates between the two spatially distinct active sites. While the aldolase is well studied, significantly less is known about the dehydrogenase. Steady-state kinetic measurements of the reverse reaction of DmpF confirmed that the dehydrogenase uses a ping-pong mechanism, with substrate inhibition by acetyl CoA indicating that NAD(+)/NADH and CoA/acetyl CoA bind to the same site in DmpF. The Km of DmpF for exogenous acetaldehyde as a substrate was 23.7 mM, demonstrating the necessity for the channel to deliver acetaldehyde directly from the aldolase to the dehydrogenase active site. A channeling assay on the bifunctional enzyme gave an efficiency of 93% indicating that less than 10% of the toxic acetaldehyde leaks out of the channel into the bulk media, prior to reaching the dehydrogenaSe active site. The thermodynamic activation parameters of the reactions catalyzed by the aldolase, the dehydrogenase and the DmpFG complex were determined. The Gibb's free energy of activation for the dehydrogenase reaction was lower than that obtained for the full DmpFG reaction, in agreement with the high K-cat obtained for the dehydrogenase reaction in isolation. Furthermore, although both the DmpF and DmpG reactions occur with small, favorable entropies of activation, the full DmpFG reaction occurs with a negative entropy of activation. This supports the concept of allosteric structural communication between the two enzymes to coordinate their activities. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.biocel.2013.05.028

文献信息

• Metabolism of 4-Amino-3-hydroxybenzoic Acid by<i>Bordetella</i>sp. Strain 10d: A Different Modified<i>Meta</i>-Cleavage Pathway for 2-Aminophenols
  作者：Chika ORII、Shinji TAKENAKA、Shuichiro MURAKAMI、Kenji AOKI

  DOI：10.1271/bbb.60264

  日期：2006.11.23

  Bordetella sp. strain 10d metabolizes 4-amino-3-hydroxybenzoic acid via 2-hydroxymuconic 6-semialdehyde. Cell extracts from 4-amino-3-hydroxybenzoate-grown cells showed high NAD+-dependent 2-hydroxymuconic 6-semialdehyde dehydrogenase, 4-oxalocrotonate tautomerase, 4-oxalocrotonate decarboxylase, and 2-oxopent-4-enoate hydratase activities, but no 2-hydroxymuconic 6-semialdehyde hydrolase activity. These enzymes involved in 4-amino-3-hydroxybenzoate metabolism were purified and characterized. When 2-hydroxymuconic 6-semialdehyde was used as substrate in a reaction mixture containing NAD+ and cell extracts from 4-amino-3-hydroxybenzoate-grown cells, 4-oxalocrotonic acid, 2-oxopent-4-enoic acid, and 4-hydroxy-2-oxovaleric acid were identified as intermediates, and pyruvic acid was identified as the final product. A complete pathway for the metabolism of 4-amino-3-hydroxybenzoic acid in strain 10d is proposed. Strain 10d metabolized 2-hydroxymuconic 6-semialdehyde derived from 4-amino-3-hydroxybenzoic acid via a dehydrogenative route, not via a hydrolytic route. This proposed metabolic pathway differs considerably from the modified meta-cleavage pathway of 2-aminophenol and those previously reported for methyl- and chloro-derivatives.

  Bordetella sp. 10d株通过2-羟基穆康酸6-半醛代谢4-氨基-3-羟基苯甲酸。来自于培养于4-氨基-3-羟基苯甲酸的细胞的细胞提取物显示出高水平的NAD+-依赖性2-羟基穆康酸6-半醛脱氢酶、4-草酰克罗通酸互变异构酶、4-草酰克罗通酸脱羧酶和2-氧戊-4-烯酸水合酶活性，但没有检测到2-羟基穆康酸6-半醛水解酶活性。这些参与4-氨基-3-羟基苯甲酸代谢的酶被纯化并进行了特征分析。当在含有NAD+和来自于4-氨基-3-羟基苯甲酸的细胞提取物的反应混合物中使用2-羟基穆康酸6-半醛作为底物时，4-草酰克罗通酸、2-氧戊-4-烯酸和4-羟基-2-氧戊酸被鉴定为中间产物，而丙酮酸被鉴定为最终产物。提出了10d株对4-氨基-3-羟基苯甲酸的完整代谢途径。10d株通过脱氢途径代谢由4-氨基-3-羟基苯甲酸衍生的2-羟基穆康酸6-半醛，而不是通过水解途径。这种提议的代谢途径与2-氨基酚的改良元断裂途径以及之前报道的甲基和氯衍生物的途径有显著不同。
• 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
• Fosdick; Rapp, Archives of Biochemistry, 1943, vol. 1, p. 387
  作者：Fosdick、Rapp

  DOI：——

  日期：——
• 10.1002/anie.202404045
  作者：Lanza, Lucrezia、Rabe von Pappenheim, Fabian、Bjarnesen, Daniela、Leogrande, Camilla、Paul, Alexandra、Krug, Leonhard、Tittmann, Kai、Müller, Michael

  DOI：10.1002/anie.202404045

  日期：——

  The thiamine diphosphate (ThDP)‐binding motif, characterized by the canonical GDG(X)24‐27N sequence, is highly conserved among ThDP‐dependent enzymes. We investigated a ThDP‐dependent lyase (JanthE from Janthinobacterium sp. HH01) with an unusual cysteine (C458) replacing the first glycine of this motif. We found that JanthE has a high substrate promiscuity accepting long aliphatic α‐keto acids as donors. Sterically hindered aromatic aldehydes or non‐activated ketones are acceptor substrates, giving access to a variety of secondary and tertiary alcohols as carboligation products. The crystal structure solved at a resolution of 1.9 Å reveals that C458 is not primarily involved in the cofactor binding as previously thought for the canonical glycine. Instead, it coordinates methionine 406, thus ensuring the integrity of the active site and the enzyme activity. We further determined the long‐sought genuine tetrahedral intermediates formed with pyruvate and 2‐oxo‐butyrate in the pre‐decarboxylation states and unravel atomic details for their stabilization in the active site. Collectively, we unravel an unexpected role for the first residue of the ThDP‐binding motif and unlock a family of lyases able to perform valuable carboligation reactions.
• [EN] MICROORGANISMS FOR PRODUCING 4C-5C COMPOUNDS WITH UNSATURATION AND METHODS RELATED THERETO<br/>[FR] MICRO-ORGANISMES POUR LA PRODUCTION DE COMPOSÉS EN 4C-5 C AVEC UNE INSATURATION ET PROCÉDÉS ASSOCIÉS
  申请人：GENOMATICA INC

  公开号：WO2016004334A1

  公开（公告）日：2016-01-07

  The invention provides a non-naturally occurring microbial organism having a butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol, pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in a pathway. The invention additionally provides a method for producing butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol,. The method can include culturing a butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol-producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding a pathway enzyme in a sufficient amount, and under conditions and for a sufficient period of time to produce butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol.

  该发明提供了一种具有丁二烯、丁烯醇、2,4-戊二烯酸酯、3-丁烯-2-醇或3-丁烯-1-醇途径的非自然微生物生物体。该微生物生物体含有至少一个编码途径中酶的外源核酸。该发明还提供了一种生产丁二烯、丁烯醇、2,4-戊二烯酸酯、3-丁烯-2-醇或3-丁烯-1-醇的方法。该方法可以包括培养一种生产丁二烯、丁烯醇、2,4-戊二烯酸酯、3-丁烯-2-醇或3-丁烯-1-醇的微生物生物体，其中该微生物生物体表达至少一个编码途径酶的外源核酸，且在足够的量下，在适当的条件和足够的时间内产生丁二烯、丁烯醇、2,4-戊二烯酸酯、3-丁烯-2-醇或3-丁烯-1-醇。