4-amino-anhydrotetracycline | 3593-53-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: 4-amino-anhydrotetracycline
• CAS: 3593-53-1
• 化学式: C₂₀H₁₈N₂O₇
• 分子量: 398.372
• InChiKey: INUFQOJZVFLXMQ-OWYOPICZSA-N

物化性质

• 沸点：
  727.0±60.0 °C(Predicted)
• 密度：
  1.713±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.15
• 重原子数：
  29.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  184.17
• 氢给体数：
  6.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-amino-anhydrotetracycline 、 S-腺苷蛋氨酸 在 OxyT from Escherichia coli 作用下， 以 phosphate buffer 为溶剂， 反应 0.17h， 生成 (4S,4aS,12aS)-3,10,11,12a-tetrahydroxy-6-methyl-4-(methylamino)-1,12-dioxo-1,4,4a,5,12,12a-hexahydrotetracene-2-carboxamide
  参考文献：
  名称：

  Identifying the Minimal Enzymes Required for Anhydrotetracycline Biosynthesis

  摘要：

  The cyclohexenone ring A of tetracyclines exhibits unique structural features not observed among other aromatic polyketides. These substitutions include the C2 primary amide, C4 dimethylamine, and the C12a tertiary alcohol. Here we report the identification and reconstitution of the minimum set of enzymes required for the biosynthesis of anhydrotetracycline (ATC, 5), the first intermediate in the tetracycline biosynthetic pathway that contains the fully functionalized ring A. Using a combination of in vivo and in vitro approaches, we confirmed OxyL, OxyQ, and OxyT to be the only enzymes required to convert 6-methylpretetramid 1 into 5. OxyL is a NADPH-dependent dioxygenase that introduces two oxygen atoms into 1 to yield the unstable intermediate 4-keto-ATC 2. The aminotransferase OxyQ catalyzes the reductive amination of C4-keto of 2, yielding 4-amino-ATC 3. Furthermore, the N,N-dimethyltransferase OxyT catalyzes the formation of 5 from 3 in a (S)-adenosylmethionine (SAM)-dependent manner. Finally, a "non-natural" anhydrotetracycline derivative was generated, demonstrating that our heterologous host/vector pair can be a useful platform toward the engineered biosynthesis of tetracycline analogues.

  DOI：

  10.1021/ja800951e
• 作为产物：
  描述：

  6-methylpretetramide 在 Streptomyces coelicolor CH₉₉₉/pWJ₂₀₉ 作用下， 生成 4,5-Dihydroxy-9-methyl-1,2-dihydrocyclopenta[b]naphthalen-3-one 、 4-amino-anhydrotetracycline
  参考文献：
  名称：

  Identifying the Minimal Enzymes Required for Anhydrotetracycline Biosynthesis

  摘要：

  The cyclohexenone ring A of tetracyclines exhibits unique structural features not observed among other aromatic polyketides. These substitutions include the C2 primary amide, C4 dimethylamine, and the C12a tertiary alcohol. Here we report the identification and reconstitution of the minimum set of enzymes required for the biosynthesis of anhydrotetracycline (ATC, 5), the first intermediate in the tetracycline biosynthetic pathway that contains the fully functionalized ring A. Using a combination of in vivo and in vitro approaches, we confirmed OxyL, OxyQ, and OxyT to be the only enzymes required to convert 6-methylpretetramid 1 into 5. OxyL is a NADPH-dependent dioxygenase that introduces two oxygen atoms into 1 to yield the unstable intermediate 4-keto-ATC 2. The aminotransferase OxyQ catalyzes the reductive amination of C4-keto of 2, yielding 4-amino-ATC 3. Furthermore, the N,N-dimethyltransferase OxyT catalyzes the formation of 5 from 3 in a (S)-adenosylmethionine (SAM)-dependent manner. Finally, a "non-natural" anhydrotetracycline derivative was generated, demonstrating that our heterologous host/vector pair can be a useful platform toward the engineered biosynthesis of tetracycline analogues.

  DOI：

  10.1021/ja800951e

文献信息

• Identifying the Minimal Enzymes Required for Anhydrotetracycline Biosynthesis
  作者：Wenjun Zhang、Kenji Watanabe、Xiaolu Cai、Michael E. Jung、Yi Tang、Jixun Zhan

  DOI：10.1021/ja800951e

  日期：2008.5.1

  The cyclohexenone ring A of tetracyclines exhibits unique structural features not observed among other aromatic polyketides. These substitutions include the C2 primary amide, C4 dimethylamine, and the C12a tertiary alcohol. Here we report the identification and reconstitution of the minimum set of enzymes required for the biosynthesis of anhydrotetracycline (ATC, 5), the first intermediate in the tetracycline biosynthetic pathway that contains the fully functionalized ring A. Using a combination of in vivo and in vitro approaches, we confirmed OxyL, OxyQ, and OxyT to be the only enzymes required to convert 6-methylpretetramid 1 into 5. OxyL is a NADPH-dependent dioxygenase that introduces two oxygen atoms into 1 to yield the unstable intermediate 4-keto-ATC 2. The aminotransferase OxyQ catalyzes the reductive amination of C4-keto of 2, yielding 4-amino-ATC 3. Furthermore, the N,N-dimethyltransferase OxyT catalyzes the formation of 5 from 3 in a (S)-adenosylmethionine (SAM)-dependent manner. Finally, a "non-natural" anhydrotetracycline derivative was generated, demonstrating that our heterologous host/vector pair can be a useful platform toward the engineered biosynthesis of tetracycline analogues.