α-ketoglutarate semialdehyde

• 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: α-ketoglutarate semialdehyde
• 英文别名: 2,5-Dioxopentanoate
• 化学式: C₅H₅O₄
• 分子量: 129.092
• InChiKey: VHKNBDIQDAXGBL-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  74.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  α-ketoglutarate semialdehyde 在 keto acid decarboxylase from Lactococcus lactis 作用下， 以 aq. buffer 为溶剂， 生成 丁二醛
  参考文献：
  名称：

  聚合转化–使用混杂的生物催化剂从异质生物质中无细胞合成化学物质

  摘要：

  已经提出了由木质纤维素生物质生产化学品的替代品。然而，生物质利用的一个固有挑战是底物的异质性，导致水解后存在混合糖。混合糖的发酵通常导致差的产量和多种副产物的产生，因此使随后的下游加工复杂化。因此，近年来已经开发了系统生物催化来应对这一挑战。在这项工作中，使用基于序列的发现方法，鉴定了几种具有广泛底物混杂的新型酶，这些酶是D-木糖和L转化的合适生物催化剂。-阿拉伯糖，植物生物量中半纤维素的两个主要成分。这些混杂酶使得D-木糖和L-阿拉伯糖能够同时进行生物转化，从而以最大的3 g L -1 h -1的产率和> 95％的产率产生1,4-丁二醇（BDO）。使用O 2作为辅因子循环的辅助底物，该模型系统进一步适应于由戊糖生产α-酮戊二酸（2-KG）的最大生产率，达到4.2 g L -1 h -1和99％的产率。为了验证我们系统的潜在适用性，我们尝试扩大D-木糖和L的BDO和2-KG产量-阿拉伯糖。

  DOI：

  10.1039/d0gc04288a
• 作为产物：
  描述：

  L-阿拉伯糖 在 β-烟酰胺腺嘌呤二核苷酸 、 L-2-keto-3-deoxy-pentonate dehydratase from Cupriavidus necator 、 lactonase-2 from Noviherbaspirillum massilense 、 xylose dehydrogenase-2 from Herbaspirillum seropedicae Z₆₇ 作用下， 以 aq. buffer 为溶剂， 生成 α-ketoglutarate semialdehyde
  参考文献：
  名称：

  聚合转化–使用混杂的生物催化剂从异质生物质中无细胞合成化学物质

  摘要：

  已经提出了由木质纤维素生物质生产化学品的替代品。然而，生物质利用的一个固有挑战是底物的异质性，导致水解后存在混合糖。混合糖的发酵通常导致差的产量和多种副产物的产生，因此使随后的下游加工复杂化。因此，近年来已经开发了系统生物催化来应对这一挑战。在这项工作中，使用基于序列的发现方法，鉴定了几种具有广泛底物混杂的新型酶，这些酶是D-木糖和L转化的合适生物催化剂。-阿拉伯糖，植物生物量中半纤维素的两个主要成分。这些混杂酶使得D-木糖和L-阿拉伯糖能够同时进行生物转化，从而以最大的3 g L -1 h -1的产率和> 95％的产率产生1,4-丁二醇（BDO）。使用O 2作为辅因子循环的辅助底物，该模型系统进一步适应于由戊糖生产α-酮戊二酸（2-KG）的最大生产率，达到4.2 g L -1 h -1和99％的产率。为了验证我们系统的潜在适用性，我们尝试扩大D-木糖和L的BDO和2-KG产量-阿拉伯糖。

  DOI：

  10.1039/d0gc04288a

文献信息

• Characterization of an <scp>l</scp>-Ascorbate Catabolic Pathway with Unprecedented Enzymatic Transformations
  作者：Tyler M. M. Stack、Katelyn N. Morrison、Thomas M. Dettmer、Brendan Wille、Chan Kim、Ryan Joyce、Madison Jermain、Yadanar Than Naing、Khadija Bhatti、Brian San Francisco、Michael S. Carter、John A. Gerlt

  DOI：10.1021/jacs.9b09863

  日期：2020.1.29

  dele-tion mutants. L-Ascorbate, a lactone, is oxidized and ring-opened by enzymes in the cytochrome b561 and gluconolactonase families, respectively, to form 2,3-diketo-L-gulonate. A protein predicted to have a WD40-like fold catalyzes an unprecedented benzilic acid rearrangement involving migration of a carboxylate group to form 2-carboxy-L-lyxonolactone; the lactone is hydrolyzed by a member of the

  L-抗坏血酸（维生素 C）在我们的饮食和环境中无处不在。在这里，我们报告了 Ralstonia eutropha H16（Cupriavidus necator ATCC 17699）通过一种新的分解代谢途径使用 L-抗坏血酸作为唯一的碳源。RNAseq 确定了 8 个候选分解代谢基因，序列相似性网络和基因组邻域网络指导对编码蛋白质功能的预测，并且这些预测通过基因缺失突变体的体外测定和体内生长表型得到证实。L-抗坏血酸是一种内酯，分别被细胞色素 b561 和葡糖酸内酯酶家族中的酶氧化和开环，形成 2,3-二酮-L-古洛糖酸。一种预测具有 WD40 样折叠的蛋白质催化了前所未有的苯甲酸重排，包括羧酸盐基团迁移形成 2-羧基-L-莱克糖内酯；内酯被酰胺水解酶超家族的一个成员水解，产生 2-羧基-L-lyxonate。PdxA 氧化脱羧酶家族的一个成员催化使用 NAD+ 催化的新型脱羧。产物 L-lyxonate
• d-Xylose Degradation Pathway in the Halophilic Archaeon Haloferax volcanii
  作者：Ulrike Johnsen、Michael Dambeck、Henning Zaiss、Tobias Fuhrer、Jörg Soppa、Uwe Sauer、Peter Schönheit

  DOI：10.1074/jbc.m109.003814

  日期：2009.10

  The pathway of D-xylose degradation in archaea is unknown. In a previous study we identified in Haloarcula marismortui the first enzyme of xylose degradation, an inducible xylose dehydrogenase (Johnsen, U., and Schonheit, P. (2004) J. Bacteriol. 186, 6198-6207). Here we report a comprehensive study of the complete D-xylose degradation pathway in the halophilic archaeon Haloferax volcanii. The analyses include the following: (i) identification of the degradation pathway in vivo following C-13-labeling patterns of proteinogenic amino acids after growth on [C-13]xylose; (ii) identification of xylose-induced genes by DNA microarray experiments; (iii) characterization of enzymes; and (iv) construction of in-frame deletion mutants and their functional analyses in growth experiments. Together, the data indicate that D-xylose is oxidized exclusively to the tricarboxylic acid cycle intermediate alpha-ketoglutarate, involving D-xylose dehydrogenase (HVO_B0028), a novel xylonate dehydratase (HVO_B0038A), 2-keto-3-deoxyxylonate dehydratase (HVO_B0027), and alpha-ketoglutarate semialdehyde dehydrogenase (HVO_B0039). The functional involvement of these enzymes in xylose degradation was proven by growth studies of the corresponding in-frame deletion mutants, which all lost the ability to grow on D-xylose, but growth on glucose was not significantly affected. This is the first report of an archaeal D-xylose degradation pathway that differs from the classical D-xylose pathway in most bacteria involving the formation of xylulose 5-phosphate as an intermediate. However, the pathway shows similarities to proposed oxidative pentose degradation pathways to alpha-ketoglutarate in few bacteria, e.g. Azospirillum brasilense and Caulobacter crescentus, and in the archaeon Sulfolobus solfataricus.
• New Insights into the Alternative d-Glucarate Degradation Pathway
  作者：Asadollah Aghaie、Christophe Lechaplais、Peggy Sirven、Sabine Tricot、Marielle Besnard-Gonnet、Delphine Muselet、Véronique de Berardinis、Annett Kreimeyer、Gabor Gyapay、Marcel Salanoubat、Alain Perret

  DOI：10.1074/jbc.m800487200

  日期：2008.6

  Although the D-glucarate degradation pathway is well characterized in Escherichia coli, genetic and biochemical information concerning the alternative pathway proposed in Pseudomonas species and Bacillus subtilis remains incomplete. Acinetobacter baylyi ADP1 is a Gram-negative soil bacterium possessing the alternative pathway and able to grow using D-glucarate as the only carbon source. Based on the annotation of its sequenced genome (1), we have constructed a complete collection of single-gene deletion mutants (2). High throughput profiling for growth on a minimal medium containing D-glucarate as the only carbon source for similar to 2450 mutants led to the identification of the genes involved in D-glucarate degradation. Protein purification after recombinant production in E. coli allowed us to reconstitute the enzymatic pathway in vitro. We describe here the kinetic characterization of D-glucarate dehydratase, D-5-keto-4-deoxyglucarate dehydratase, and of cooperative alpha-ketoglutarate semialdehyde dehydrogenase. Transcription and expression analyses of the genes involved in D-glucarate metabolism within a single organism made it possible to access information regarding the regulation of this pathway for the first time.
• A Novel α-Ketoglutaric Semialdehyde Dehydrogenase
  作者：Seiya Watanabe、Tsutomu Kodaki、Keisuke Makino

  DOI：10.1074/jbc.m602585200

  日期：2006.9

  Azospirillum brasilense possesses an alternative pathway of L-arabinose metabolism, which is different from the known bacterial and fungal pathways. In a previous paper (Watanabe, S., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 2612-2623), we identified and characterized L-arabinose 1-dehydrogenase, which catalyzes the first reaction step in this pathway, and we cloned the corresponding gene. Here we focused on the fifth enzyme, alpha-ketoglutaric semialdehyde (alpha KGSA) dehydrogenase, catalyzing the conversion of alpha KGSA to alpha-ketoglutarate. alpha KGSA dehydrogenase was purified tentatively as a NAD(+)-preferring aldehyde dehydrogenase (ALDH) with high activity for glutaraldehyde. The gene encoding this enzyme was cloned and shown to be located on the genome of A. brasilense separately from a gene cluster containing the L-arabinose 1-dehydrogenase gene, in contrast with Burkholderia thailandensis in which both genes are located in the same gene cluster. Higher catalytic efficiency of ALDH was found with alpha KGSA and succinic semialdehyde among the tested aldehyde substrates. In zymogram staining analysis with the cell-free extract, a single active band was found at the same position as the purified enzyme. Furthermore, a disruptant of the gene did not grow on L-arabinose. These results indicated that this ALDH gene was the only gene of the NAD(+)-preferring alpha KGSA dehydrogenase in A. brasilense. In the phylogenetic tree of the ALDH family, alpha KGSA dehydrogenase from A. brasilense falls into the succinic semialdehyde dehydrogenase (SSALDH) subfamily. Several putative alpha KGSA dehydrogenases from other bacteria belong to a different ALDH subfamily from SSALDH, suggesting strongly that their substrate specificities for alpha KGSA are acquired independently during the evolutionary stage. This is the first evidence of unique "convergent evolution" in the ALDH family.
• Identification and Characterization of l-Arabonate Dehydratase, l-2-Keto-3-deoxyarabonate Dehydratase, and l-Arabinolactonase Involved in an Alternative Pathway of l-Arabinose Metabolism
  作者：Seiya Watanabe、Naoko Shimada、Kunihiko Tajima、Tsutomu Kodaki、Keisuke Makino

  DOI：10.1074/jbc.m606727200

  日期：2006.11

  Azospirillum brasiliense possesses an alternative pathway of L-arabinose metabolism, different from the known bacterial and fungal pathways. In the preceding articles, we identified and characterized L-arabinose-1-dehydrogenase and alpha-ketoglutaric semialdehyde dehydrogenase, which catalyzes the first and final reaction steps in this pathway, respectively (Watanabe, S., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 2612-2623 and Watanabe, S., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 28876-28888). We here report the remaining three enzymes, L-arabonate dehydratase, L-2-keto-3-deoxyarabonate (L-KDA) dehydratase, and L-arabinolactonase. N-terminal amino acid sequences of L-arabonate dehydratase and L-KDA dehydratase purified from A. brasiliense cells corresponded to those of AraC and AraD genes, which form a single transcriptional unit together with the L-arabinose-1-dehydrogenase gene. Furthermore, the L-arabinolactonase gene (AraB) was also identified as a component of the gene cluster. Genetic characterization of the alternative L-arabinose pathway suggested a significant evolutional relationship with the known sugar metabolic pathways, including the Entner-Doudoroff (ED) pathway and the several modified versions. L-Arabonate dehydratase belongs to the ILVD/EDD family and spectrophotometric and electron paramagnetic resonance analysis revealed it to contain a [4Fe-4S]2(+) cluster. Site-directed mutagenesis identified three cysteine ligands essential for cluster coordination. L-KDA dehydratase was sequentially similar to DHDPS/NAL family proteins. D-2-Keto-3-deoxygluconate aldolase, a member of the DHDPS/NAL family, catalyzes the equivalent reaction to L-KDA aldolase involved in another alternative L-arabinose pathway, probably associating a unique evolutional event between the two alternative L-arabinose pathways by mutation(s) of a common ancestral enzyme. Site-directed mutagenesis revealed a unique catalytic amino acid residue in L-KDA dehydratase, which may be a candidate for such a natural mutation.