(2R,3S)-3-isopropylmalic acid | 126576-14-5

• 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: (2R,3S)-3-isopropylmalic acid
• 英文别名: (2R,3S)-3-isopropylmalate；(2R,3S)-threo-Ds-3-isopropylmalic acid；3-Isopropylmalic acid；(2R,3S)-2-hydroxy-3-propan-2-ylbutanedioic acid
• CAS: 126576-14-5
• 化学式: C₇H₁₂O₅
• 分子量: 176.169
• InChiKey: RNQHMTFBUSSBJQ-CRCLSJGQSA-N

物化性质

• 熔点：
  146-147 °C
• 沸点：
  306.4±27.0 °C(Predicted)
• 密度：
  1.334±0.06 g/cm3(Predicted)
• 物理描述：
  Solid
• 碰撞截面：
  127.46 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3S)-3-isopropylmalic acid 在 mutant 3-isopropylmalate dehydrogenase(Gly₈₉ changed to Ser) 、 nicotinamide adenine dinucleotide 作用下， 以 水 为溶剂， 生成 4-甲基-2-氧代戊酸
  参考文献：
  名称：

  Novel Substrate Specificity of Designer 3-Isopropylmalate Dehydrogenase Derived from Thermus thermophilus HB8

  摘要：

  对酶进行重新设计以适应新的催化反应并修改底物特异性，采用了3-异丙基苹果酸脱氢酶（IPMDH）。通过将Gly-89（不在催化位点但靠近它）突变为Ala、Ser、Val和Pro，进行了点突变，所有突变均改变了底物特异性。当以苹果酸作为底物而不是3-异丙基苹果酸时，突变酶的催化效率（kcat/Km）高于天然IPMDH。更有趣的是，在Gly-89和Leu-90之间额外插入Gly显著改变了底物特异性，尽管整体催化活性下降。特别是，这个突变体有效地接受D-乳酸，而野生型IPMDH根本不接受该底物。这些结果表明，通过修改不直接参与催化的氨基酸残基或插入额外的残基，有机会创造出新型酶。

  DOI：

  10.1271/bbb.65.2695
• 作为产物：
  描述：

  1-lithio-3-methyl-1-butyne 在 Lindlar's catalyst sodium hydroxide 、 lithium aluminium tetrahydride 、 氢气 、 臭氧 、 lithium diisopropyl amide 作用下， 以 二甲基亚砜 为溶剂， 反应 0.17h， 生成 (2R,3S)-3-isopropylmalic acid
  参考文献：
  名称：

  [2,3]-碳水化合物模板上的维蒂希重排。手性合成3-烷基苹果酸的新方法

  摘要：

  碳水化合物模板上的叔α-（烯丙氧基）-乙酸体系的Dianion [2,3] -Wittig重排已实现有效的手性转移，从而提供了3-烷基苹果酸的非对映选择性手性合成。

  DOI：

  10.1016/s0040-4039(00)99347-x

文献信息

• Overproduction and Substrate Specificity of 3-Isopropylmalate Dehydrogenase from<i>Thiobacillus ferrooxidans</i>
  作者：Hideyuki MATSUNAMI、Hiroshi KAWAGUCHI、Kenji INAGAKI、Tadashi EGUCHI、Katsumi KAKINUMA、Hidehiko TANAKA

  DOI：10.1271/bbb.62.372

  日期：1998.1

  We constructed an overexpression system in Escherichia coli of the leuB gene coding for 3-isopropylmalate dehydrogenase in Thiobacillus ferrooxidans. E. coli harboring the plasmid we constructed, pKK leuB1, produced 17-fold the enzyme protein of the expression system previously used for purification. The substrate specificity of the enzyme was analyzed with synthetic (2R, 3S)-3-alkylmalates. The 3-isopropylmalate dehydrogenase of Thiobacillus ferrooxidans had broad specificity toward the alkylmalates.

  我们在大肠杆菌中构建了一个超表达系统，该系统中的leuB基因编码硫杆菌铁氧体中的3-异丙基丙二酸脱氢酶。携带我们构建的质粒 pKK leuB1 的大肠杆菌产生的酶蛋白是以前用于纯化的表达系统的 17 倍。用合成的（2R，3S）-3-烷基丙二酸盐分析了该酶的底物特异性。铁氧化硫杆菌的 3-异丙基丙二酸脱氢酶对烷基丙二酸盐具有广泛的特异性。
• Coenzyme Activity of NAD Analogs for 3-Isopropylmalate Dehydrogenase from<i>Thermus thermophilus</i>HB8
  作者：Akira CHIBA、Tadashi EGUCHI、Tairo OSHIMA、Katsumi KAKINUMA

  DOI：10.1271/bbb.63.1647

  日期：1999.1

  In order to elucidate the enzyme-substrate-cofactor interaction in 3-isopropylmalate dehydrogenase, the coenzyme activity of NAD analogs which have a 3-substituted pyridine ring was examined. Analogs 3-5 showed diminished kcat values compared with those of NAD+, whereas thiocarboxamide 2 was almost as equally active as NAD+. This suggests that the NH2 functionality of NAD+ is more important for the catalysis of IPMDH than a carbonyl group.

  为了阐明三异丙基苹果酸脱氢酶中的酶-底物-辅因子相互作用，研究了具有3取代吡啶环的NAD类似物的辅酶活性。类似物3-5的kcat值相比于NAD+有所降低，而硫羧酰胺2的活性几乎与NAD+相当。这表明，NAD+的NH2功能对于IPMDH的催化比羰基更为重要。
• Synthesis of isoprenoids and derivatives
  申请人：William Marsh Rice University

  公开号：US11046978B2

  公开（公告）日：2021-06-29

  This disclosure generally relates to the use of enzyme combinations or recombinant microbes comprising same to make isoprenoid precursors, isoprenoids and derivatives thereof including prenylated aromatic compounds. Novel metabolic pathways exploiting Claisen, aldol, and acyioin condensations are used instead of the natural mevalonate (MVA) pathway or 1-deoxy-d-xylulose 5-phosphate (DXP) pathways for generating isoprenoid precursors such as isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), and geranyl pyrophosphate (GPP). These pathways have the potential for better carbon and or energy efficiency than native pathways. Both decarboxylative and non-carboxylative condensations are utilized, enabling product synthesis from a number of different starting compounds. These condensation reactions serve as a platform for the synthesis of isoprenoid precursors when utilized in combination with a variety of metabolic pathways and enzymes for carbon rearrangement and the addition/removal of functional groups. Isoprenoid alcohols are key intermediary products for the production of isoprenoid precursors in these novel synthetic metabolic pathways.

  本公开内容一般涉及使用酶组合或包含酶组合的重组微生物来制造异戊烯前体、异戊烯及其衍生物，包括前炔基芳香族化合物。利用克来森缩合、醛醇缩合和酰亚胺缩合的新型代谢途径取代了天然的甲羟戊酸（MVA）途径或 1-脱氧-d-木酮糖-5-磷酸（DXP）途径，用于生成焦磷酸异戊烯酯（IPP）、焦磷酸二甲基烯丙基酯（DMAPP）和焦磷酸香叶酯（GPP）等异戊烯前体。与原生途径相比，这些途径具有更高的碳效率和能量效率。利用脱羧和非羧缩合反应，可以从多种不同的起始化合物中合成产品。这些缩合反应可作为合成异戊二烯前体的平台，与各种代谢途径和酶结合使用，进行碳重排和官能团的添加/去除。在这些新型合成代谢途径中，异戊二烯醇是生产异戊二烯前体的关键中间产物。
• Substrate Specificity Determinants of the Methanogen Homoaconitase Enzyme: Structure and Function of the Small Subunit^,
  作者：Jeyaraman Jeyakanthan、Randy M. Drevland、Dasara Raju Gayathri、Devadasan Velmurugan、Akeo Shinkai、Seiki Kuramitsu、Shigeyuki Yokoyama、David E. Graham

  DOI：10.1021/bi901766z

  日期：2010.3.30

  The aconitase family of hydro-lyase enzymes includes three classes of proteins that catalyze the isomerization of alpha-hydroxy acids to beta-hydroxy acids. Besides aconitase, isopropylmalate isomerase (IPMI) proteins specifically catalyze the isomerization of alpha,beta-dicarboxylates with hydrophobic gamma-chain groups, and homoaconitase (HACN) proteins catalyze the isomerization of tricarboxylates with variable chain length gamma-carboxylate groups. These enzymes' stereospecific hydro-lyase activities make them attractive catalysts to produce diastereomers from unsaturated precursors. However, sequence similarity and convergent evolution among these proteins lead to widespread misannotation and uncertainty about gene function. To Find the substrate specificity determinants of homologous IPMI and HACN proteins from Methanocaldococcus jannaschii, the small-subunit HACN protein (MJ1271) was crystallized for X-ray diffraction. The Structural model showed characteristic residues in a flexible loop region between alpha 2 and alpha 3 that distinguish HACN from IPMI and aconitase proteins. Site-directed mutagenesis of MJ1271 produced loop-region variant proteins that were reconstituted with wild-type MJ1003 large-subunit protein. The heteromers formed promiscuous hydro-lyases with reduced activity but broader substrate specificity. Both R26K and R26V variants formed relatively efficient IPMI enzymes, while the T27A variant had uniformly lower specificity constants for both IPMI and HACN substrates. The R26V T27Y variant resembles the MJ1277 IPMI small subunit in its flexible loop sequence but demonstrated the broad substrate specificity of the R26V variant. These mutations may reverse the evolution of HACN activity from an ancestral IPMI gene, demonstrating the evolutionary potential for promiscuity in hydro-lyase enzymes. Understanding these specificity determinants enables the functional reannotation of paralogous HACN and IPMI genes in numerous genome sequences. These structural and kinetic results will help to engineer new stereospecific hydro-lyase enzymes for chemoenzymatic syntheses.
• Kakinuma, Katsumi; Terasawa, Hiroaki; Li, Hui-Ying, Bioscience, Biotechnology and Biochemistry, 1993, vol. 57, # 11, p. 1916 - 1923
  作者：Kakinuma, Katsumi、Terasawa, Hiroaki、Li, Hui-Ying、Miyazaki, Kentaro、Oshima, Tairo

  DOI：——

  日期：——