[R]-α-hydroxy-isovalerate

• 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: [R]-α-hydroxy-isovalerate
• 英文别名: (R)-3-methyl-2-hydroxybutanoate；[R]-2-hydroxyisovalerate；2-(R)-hydroxyisovalerat；(2R)-2-hydroxy-3-methylbutanoate
• 化学式: C₅H₉O₃
• 分子量: 117.125
• InChiKey: NGEWQZIDQIYUNV-SCSAIBSYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [R]-α-hydroxy-isovalerate 、 NADP⁺ 生成 2-ketoisovalerate 、 氢(+1)阳离子 、 NADPH(4-)
  参考文献：
  名称：

  球孢白僵菌（Beauveria bassiana）的加扰的白僵菌素，环果寡糖二肽细胞迁移抑制剂的组合诱变

  摘要：

  炒缩肽：我们展示了一个新的变种mutasynthesis技术。将前体类似物组合同时喂入球孢白僵菌菌株中，并在新鉴定的酮异戊酸还原酶基因中有针对性地敲除，从而产生具有改变的细胞迁移抑制活性的非天然beauvericins。

  DOI：

  10.1002/cbic.200800570
• 作为产物：
  描述：

  (2R)-acetoxy-3-methylbutanoate 在 citrate synthase 、 acetyl-CoA synthetase 、 Agrobacterium tumefaciens C₅₈ recombinant Atu₃₂₆₆ protein 、 L-malate dehydrogenase 、 β-烟酰胺腺嘌呤二核苷酸 、 水 、 5’-三磷酸腺苷 、 辅酶 A 、 magnesium chloride 作用下， 生成 [R]-α-hydroxy-isovalerate
  参考文献：
  名称：

  Functional Annotation and Three-Dimensional Structure of an Incorrectly Annotated Dihydroorotase from cog3964 in the Amidohydrolase Superfamily

  摘要：

  The substrate specificities of two incorrectly annotated enzymes belonging to cog3964 from the amidohydrolase superfamily were determined. This group of enzymes are currently misannotated as either dihydroorotases or adenine deaminases. Atu3266 from Agrobacterium tumefaciens C58 and Oant2987 from Ochrobactrum anthropi ATCC 49188 were found to catalyze the hydrolysis of acetyl-(R)-mandelate and similar esters with values of K-cat/K-m that exceed 10(5) M-1 s(-1). These enzymes do not catalyze the deamination of adenine or the hydrolysis of dihydroorotate. Atu3266 was crystallized and the structure determined to a resolution of 2.62 angstrom. The protein folds as a distorted (beta/alpha)(8) barrel and binds two zincs in the active site. The substrate profile was determined via a combination of computational docking to the three-dimensional structure of Atu3266 and screening of a highly focused library of potential substrates. The initial weak hit was the hydrolysis of N-acetyl-D-serine (k(cat)/K-m = 4 M-1 s(-1)). This was followed by the progressive identification of acetyl-(R)-glycerate (k(cat)/K-m = 4 x 10(2) M-1 s(-1)), acetyl glycolate (k(cat)/K-m = 1.3 x 10(4) M-1 s(-1)), and ultimately acetyl-(R)-mandelate (k(cat)/K-m = 2.8 x 10(2) M-1 s(-1)).

  DOI：

  10.1021/bi301483z

文献信息

• Harnessing fungal nonribosomal cyclodepsipeptide synthetases for mechanistic insights and tailored engineering
  作者：Charlotte Steiniger、Sylvester Hoffmann、Andi Mainz、Marcel Kaiser、Kerstin Voigt、Vera Meyer、Roderich D. Süssmuth

  DOI：10.1039/c7sc03093b

  日期：——

  Hybrid fungal CDP synthetases are constructed from three different origins to produce highly active cyclodepsipeptides up to g L⁻¹ scale.

  混合真菌CDP合成酶是由三种不同来源构建的，以产生高活性的环状肽类物质，可达到g/L级别。
• Combinatorial Mutasynthesis of Scrambled Beauvericins, Cyclooligomer Depsipeptide Cell Migration Inhibitors from<i>Beauveria bassiana</i>
  作者：Yuquan Xu、E. M. Kithsiri Wijeratne、Patricia Espinosa-Artiles、A. A. Leslie Gunatilaka、István Molnár

  DOI：10.1002/cbic.200800570

  日期：2009.1.26

  Scrambled depsipeptides: We demonstrate a novel variant mutasynthesis technique. Combinatorial simultaneous feeding of precursor analogues to a Beauveria bassiana strain with a targeted knockout in the newly identified ketoisovalerate reductase gene yields unnatural beauvericins with altered cell migration inhibitory activities.

  炒缩肽：我们展示了一个新的变种mutasynthesis技术。将前体类似物组合同时喂入球孢白僵菌菌株中，并在新鉴定的酮异戊酸还原酶基因中有针对性地敲除，从而产生具有改变的细胞迁移抑制活性的非天然beauvericins。
• Functional dissection and module swapping of fungal cyclooligomer depsipeptide synthetases
  作者：Dayu Yu、Fuchao Xu、David Gage、Jixun Zhan

  DOI：10.1039/c3cc42425a

  日期：——

  BbBSLS and BbBEAS were dissected and reconstituted in Saccharomyces cerevisiae. The intermodular linker is essential for the reconstitution of the separate modules. Module 1 can be swapped between BbBEAS and BbBSLS, while modules 2 and 3 control the product profiles. BbBSLS is a flexible enzyme that also synthesizes beauvericins.

  BbBSLS和BbBEAS在酿酒酵母中被分解和重组。模块间连接剂对于重组单独模块至关重要。模块1可在BbBEAS和BbBSLS之间互换，而模块2和3则控制产品特征。BbBSLS是一种可合成鲍氏青霉素的柔性酶。
• Modified substrate specificity of a methyltransferase domain by protein insertion into an adenylation domain of the bassianolide synthetase
  作者：Fuchao Xu、Russell Butler、Kyle May、Megi Rexhepaj、Dayu Yu、Jiachen Zi、Yi Chen、Yonghong Liang、Jia Zeng、Joan Hevel、Jixun Zhan

  DOI：10.1186/s13036-019-0195-y

  日期：2019.12

  not recover bassianolide biosynthesis. In order to address the functional implications of the protein insertion, we characterized the N-methyltransferase activity of the MT domain as both the isolated domain (MTBSLS) and as part of the full NRPS megaenzyme. Surprisingly, the MTBSLS construct demonstrated a relaxed substrate specificity and preferentially methylated an amino acid (L-Phe-SNAC) that is rarely

  背景使用来自聚酮化合物合成酶和/或非核糖体肽合成酶（NRPS）的选择结构域的组合创建设计分子仍然是一个合成目标。然而，对蛋白质-蛋白质相互作用和动力学如何影响每个域功能的不完全理解是该领域的主要障碍。特别感兴趣的是了解一类甲基转移酶结构域 (MT) 的基础，这些结构域嵌入在真菌 NRPS 系统的腺苷酸化结构域 (A) 中，而不是在端到端架构中。结果去除了basianolide合成酶(BSLS)的MT结构域，重组表达了截短酶BSLS-ΔMT。取消了bassianolide的生物合成，N-去甲基bassianolide的产量很低。BSLS-ΔMT 与独立 MT 的共表达没有恢复巴西亚诺内酯的生物合成。为了解决蛋白质插入的功能影响，我们将 MT 结构域的 N-甲基转移酶活性表征为分离结构域 (MTBSLS) 和完整 NRPS 巨酶的一部分。令人惊讶的是，MTBSLS 构建体表现出宽松的底物特异性，并优先将很少掺入最终产物的氨基酸
• Lee C.; Gorisch H.; Kleinkauf H., J Biol Chem, 1992, 0021-9258, 11741-4
  作者：Lee C.、Gorisch H.、Kleinkauf H.、Zocher R.

  DOI：——

  日期：——