N-methyl-L-valyl-L-tryptophanol | 102141-01-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-methyl-L-valyl-L-tryptophanol
• 英文别名: n-Methyl-l-valyl-l-tryptophanol；(2S)-N-[(2S)-1-hydroxy-3-(1H-indol-3-yl)propan-2-yl]-3-methyl-2-(methylamino)butanamide
• CAS: 102141-01-5
• 化学式: C₁₇H₂₅N₃O₂
• 分子量: 303.404
• InChiKey: OQYFURUBPANIIX-BBRMVZONSA-N

物化性质

• 沸点：
  576.8±50.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  77.2
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-methyl-L-valyl-L-tryptophanol 在 cytochrome P₄₅₀ monooxygenase 、 teleocidin B 、 氧气 、 CamA from Pseudomonas putida 、 CamB from Pseudomonas putida 、 还原型辅酶Ⅰ 、 catalase 作用下， 以 aq. buffer 为溶剂， 生成 吲哚内酰胺 V
  参考文献：
  名称：

  利用CN键形成细胞色素P450单加氧酶进行CS键形成。

  摘要：

  CS键形成反应广泛地分布在生物活性分子的生物合成中，因此在过去的几十年中受到了广泛的关注。在本文中，我们报道了通过P450单加氧酶TleB分子内CS键的形成，该酶通常会在Teleocidin生物合成中催化CN键的形成。根据拟议的TleB反应机理，合成并测试了巯基取代的底物类似物，并在酶反应中进行了测试，除具有不寻常的吲哚稠合的6/5 / 8-外，还提供了前所未有的含硫硫代吲哚内酰胺V。通过结晶海绵法确定其结构的三环产物。有趣的是，构象分析表明，SOFA构象在硫代吲哚内酰胺V中是稳定的，这与吲哚内酰胺V中的主要TWIST形式形成鲜明对比，

  DOI：

  10.1002/anie.201916269
• 作为产物：
  描述：

  在 乙二胺四乙酸 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 phosphate buffer 为溶剂， 反应 0.5h， 生成 N-methyl-L-valyl-L-tryptophanol 、 N-Me-L-Val-L-Trp
  参考文献：
  名称：

  The Lyngbyatoxin Biosynthetic Assembly Line:  Chain Release by Four-Electron Reduction of a Dipeptidyl Thioester to the Corresponding Alcohol

  摘要：

  In comparison with the large number of nonribosomal peptide synthetases (NRPSs) that release their peptide products by hydrolytic cleavage of the peptide carrier Protein (PCP) bound thioester, there are relatively few NRPSs that have been shown to use a nicotinamide cofactor to reduce this PCP-peptidyl thioester to an aldehyde or imine moiety, This work describes the first example of a reductase domain within a NRPS scaffold shown to reduce a PCP-pepbdyl thioester to the corresponding primary alcohol, via an aldehyde intermediate, using two equivalents of reduced nicotinamide adenine dinucleotide phosphate (NADPH). By employing a ketone mimic of the aldehyde intermediate, as well as a specifically deuterated NADPH, it was further demonstrated that the pro-S hydride of the cofactor is transferred to the re face of the carbonyl group.

  DOI：

  10.1021/ja077374d

文献信息

• Enzymatic Production of (−)-Indolactam V by LtxB, a Cytochrome P450 Monooxygenase
  作者：Minh U. Huynh、Matthew C. Elston、Nick M. Hernandez、David B. Ball、Shin-ichiro Kajiyama、Kazuhiro Irie、William H. Gerwick、Daniel J. Edwards

  DOI：10.1021/np900481a

  日期：2010.1.22

  The P450 cytochrome monooxygenase gene, ltxB, was cloned and overexpressed in Escherichia coli as a 6xHis-taoged protein. The resulting recombinant LtxB was purified by Ni-NTA affinity chromatography and characterized biochemically. Purified LtxB demonstrated typical cytochrome P450 spectroscopic properties including substrate-induced transition from a low-spin (lambda(max) = 414 nm) to high-spin state (lambda(max) = 386 nm) upon incubation with N-methyl-L-valyl-L-tryptophanol. The catalytic activity of LtxB was verified by demonstrating the oxidation/cyclization of N-methyl-L-valyl-L-tryptophanol to (-)-indolactam V. LtxB shows a relaxed specificity for analogue substrates in which the valyl group is substituted for other aliphatic groups. The relaxed substrate specificity of LtxB, along with the relaxed specificity of the prenyltransferase, LtxC, allowed for the enzymatic production of a series of (-)-indolactam V and lyngbyatoxin analogues.
• The Lyngbyatoxin Biosynthetic Assembly Line:  Chain Release by Four-Electron Reduction of a Dipeptidyl Thioester to the Corresponding Alcohol
  作者：Jay A. Read、Christopher T. Walsh

  DOI：10.1021/ja077374d

  日期：2007.12.1

  In comparison with the large number of nonribosomal peptide synthetases (NRPSs) that release their peptide products by hydrolytic cleavage of the peptide carrier Protein (PCP) bound thioester, there are relatively few NRPSs that have been shown to use a nicotinamide cofactor to reduce this PCP-peptidyl thioester to an aldehyde or imine moiety, This work describes the first example of a reductase domain within a NRPS scaffold shown to reduce a PCP-pepbdyl thioester to the corresponding primary alcohol, via an aldehyde intermediate, using two equivalents of reduced nicotinamide adenine dinucleotide phosphate (NADPH). By employing a ketone mimic of the aldehyde intermediate, as well as a specifically deuterated NADPH, it was further demonstrated that the pro-S hydride of the cofactor is transferred to the re face of the carbonyl group.
• Exploiting a C–N Bond Forming Cytochrome P450 Monooxygenase for C–S Bond Formation
  作者：Iori Morita、Takahiro Mori、Takaaki Mitsuhashi、Shotaro Hoshino、Yoshimasa Taniguchi、Takashi Kikuchi、Kei Nagae、Norihiro Nasu、Makoto Fujita、Tomohiko Ohwada、Ikuro Abe

  DOI：10.1002/anie.201916269

  日期：2020.3.2

  C-S bond formation reactions are widely distributed in the biosynthesis of biologically active molecules, and thus have received much attention over the past decades. Herein, we report intramolecular C-S bond formation by a P450 monooxygenase, TleB, which normally catalyzes a C-N bond formation in teleocidin biosynthesis. Based on the proposed reaction mechanism of TleB, a thiol-substituted substrate

  CS键形成反应广泛地分布在生物活性分子的生物合成中，因此在过去的几十年中受到了广泛的关注。在本文中，我们报道了通过P450单加氧酶TleB分子内CS键的形成，该酶通常会在Teleocidin生物合成中催化CN键的形成。根据拟议的TleB反应机理，合成并测试了巯基取代的底物类似物，并在酶反应中进行了测试，除具有不寻常的吲哚稠合的6/5 / 8-外，还提供了前所未有的含硫硫代吲哚内酰胺V。通过结晶海绵法确定其结构的三环产物。有趣的是，构象分析表明，SOFA构象在硫代吲哚内酰胺V中是稳定的，这与吲哚内酰胺V中的主要TWIST形式形成鲜明对比，