dapdiamide A | 1196054-26-8

• 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: dapdiamide A
• 英文别名: (2S)-2-{[(2S)-3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-2-azaniumylpropanoyl]amino}-3-methylbutanoate；(2S)-2-[[(2S)-3-[[(E)-4-amino-4-oxobut-2-enoyl]amino]-2-azaniumylpropanoyl]amino]-3-methylbutanoate
• CAS: 1196054-26-8
• 化学式: C₁₂H₂₀N₄O₅
• 分子量: 300.315
• InChiKey: JAGLEOBXISHNNM-BRUQVKLWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.2
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  165
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-tert-butyl 2-((S)-3-((E)-4-amino-4-oxobut-2-enamido)-2-(tert-butoxycarbonylamino)propanamido)-3-methylbutanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 dapdiamide A
  参考文献：
  名称：

  Dapdiamides, Tripeptide Antibiotics Formed by Unconventional Amide Ligases

  摘要：

  Construction of a genomic DNA library from Pantoea agglomerans strain CU0119 and screening against the plant pathogen Erwinia amylovora yielded a new family of antibiotics, dapdiamides A-E (1-5). The structures were established through 2D-NMR experiments and mass spectrometry, as well as the synthesis of dapdiamide A (1). Transposon mutagenesis of the active cosmid allowed identification of the biosynthetic gene cluster. The dapdiamide family's promiscuous biosynthetic pathway contains two unconventional amide ligases that are predicted to couple its constituent monomers.

  DOI：

  10.1021/np900685z

文献信息

• The Nonribosomal Peptide Synthetase Enzyme DdaD Tethers <i>N</i>_β-Fumaramoyl-<scp>l</scp>-2,3-diaminopropionate for Fe(II)/α-Ketoglutarate-Dependent Epoxidation by DdaC during Dapdiamide Antibiotic Biosynthesis
  作者：Marie A. Hollenhorst、Stefanie B. Bumpus、Megan L. Matthews、J. Martin Bollinger、Neil L. Kelleher、Christopher T. Walsh

  DOI：10.1021/ja1072367

  日期：2010.11.10

  The gene cluster from Pantoea agglomerans responsible for biosynthesis of the dapdiamide antibiotics encodes an adenylation-thiolation didomain protein, DdaD, and an Fe(II)/α-ketoglutarate-dependent dioxygenase homologue, DdaC. Here we show that DdaD, a nonribosomal peptide synthetase module, activates and sequesters N(β)-fumaramoyl-l-2,3-diaminopropionate as a covalently tethered thioester for subsequent

  来自成团泛菌的基因簇负责 dapdiamide 抗生素的生物合成，编码腺苷酸化-硫醇化双结构域蛋白 DdaD 和 Fe(II)/α-酮戊二酸依赖性双加氧酶同源物 DdaC。在这里，我们展示了 DdaD，一种非核糖体肽合成酶模块，激活和隔离 N(β)-延胡索酰基-1-2,3-二氨基丙酸酯作为共价连接的硫酯，用于随后对延胡索酰基进行氧化修饰。DdaC 催化共价结合的 N(β)-富马甲酰基-1-2,3-二氨基丙酰基-S-DdaD 物质的 Fe(II)-和 α-酮戊二酸依赖性环氧化，生成 N(β)-环氧琥珀酰胺-DAP (DAP = 2,3-二氨基丙酸酯）与 DdaD 的硫酯连接。水解释放后，
• The ATP-Dependent Amide Ligases DdaG and DdaF Assemble the Fumaramoyl-Dipeptide Scaffold of the Dapdiamide Antibiotics
  作者：Marie A. Hollenhorst、Jon Clardy、Christopher T. Walsh

  DOI：10.1021/bi9013165

  日期：2009.11.3

  The enzymes DdaG and DdaF, encoded in the Pantoea agglomerans dapdiamide antibiotic biosynthetic gene cluster, when expressed in Escherichia coli, form the tandem amide bonds of the dapdiamide scaffold at the expense of ATP cleavage. DdaG uses fumarate, 2,3-diaminopropionate (DAP), and ATP to make fumaroyl-AMP transiently on the way to the Nβ-fumaroyl-DAP regioisomer. Then DdaF acts as a second ATP-dependent

  当在大肠杆菌中表达时，在成团泛菌dapdiamide 抗生素生物合成基因簇中编码的 DdaG 和 DdaF 酶以 ATP 裂解为代价形成 dapdiamide 支架的串联酰胺键。DdaG 使用富马酸酯、2,3-二氨基丙酸酯 (DAP) 和 ATP 在生成N β -富马酰-DAP 区域异构体的过程中瞬时生成富马酰-AMP 。然后 DdaF 充当第二个 ATP 依赖性酰胺连接酶，但该酶在酰胺键形成过程中将 ATP 裂解为 ADP 和 P i。但是，DdaF 不接受N β -富马酰-DAP；该酶需要富马酰基部分首先转化为N β 中的富马酰基半酰胺-富马酰基-DAP。DdaF 将 Val、Ile 或 Leu 添加到富马甲酰基-DAP 的羧酸盐中，分别制备达帕二胺 A、B 或 C。因此，为了构建 dapdiamide 抗生素支架，在 DdaG 作用之后但在 DdaF 催化之前，富马酰-DAP 支架上
• Dapdiamides, Tripeptide Antibiotics Formed by Unconventional Amide Ligases
  作者：Jessica Dawlaty、Xiaorong Zhang、Michael A. Fischbach、Jon Clardy

  DOI：10.1021/np900685z

  日期：2010.3.26

  Construction of a genomic DNA library from Pantoea agglomerans strain CU0119 and screening against the plant pathogen Erwinia amylovora yielded a new family of antibiotics, dapdiamides A-E (1-5). The structures were established through 2D-NMR experiments and mass spectrometry, as well as the synthesis of dapdiamide A (1). Transposon mutagenesis of the active cosmid allowed identification of the biosynthetic gene cluster. The dapdiamide family's promiscuous biosynthetic pathway contains two unconventional amide ligases that are predicted to couple its constituent monomers.