4-Hydroxy-6-methyl-pretetramid | 2011-31-6

• 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-Hydroxy-6-methyl-pretetramid
• 英文别名: 4-Hydroxy-6-methyl-praetetramid；1,3,4,10,11,12-Hexahydroxy-6-methyltetracene-2-carboxamide
• CAS: 2011-31-6
• 化学式: C₂₀H₁₅NO₇
• 分子量: 381.342
• InChiKey: WSYJHDYOVBGOSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  165
• 氢给体数：
  7
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-Hydroxy-6-methyl-pretetramid 、 NADPH(4-) 、 氧气 生成 4-Dedimethylamino-4-oxo-anhydrotetracycline 、 水 、 NADP⁺
  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(1-) 、 氢(+1)阳离子 、 NADPH(4-) 、 氧气 生成 4-Hydroxy-6-methyl-pretetramid 、 水 、 NADP⁺
  参考文献：
  名称：

  四环素生物合成过程中OxyE作为辅助加氧酶的鉴定

  摘要：

  辅助加氧酶：OxyE被认为是在金黄色链霉菌中土霉素的生物合成过程中使用的一种可能的辅助C-4羟化酶。氧化酶OxyE和OxyL的协同作用可确保完全的氧化调节，并防止生物合成中间体的不可逆分流修饰。

  DOI：

  10.1002/cbic.200900122

文献信息

• Processes and host cells for genome, pathway, and biomolecular engineering
  申请人：enEvolv, Inc.

  公开号：US10370654B2

  公开（公告）日：2019-08-06

  The present disclosure provides compositions and methods for genomic engineering.

  本公开提供了基因组工程的组合物和方法。
• PROCESSES AND HOST CELLS FOR GENOME, PATHWAY, AND BIOMOLECULAR ENGINEERING
  申请人：ENEVOLV, INC.

  公开号：US20160186168A1

  公开（公告）日：2016-06-30

  The present disclosure provides compositions and methods for genomic engineering.
• US9944925B2
  申请人：——

  公开号：US9944925B2

  公开（公告）日：2018-04-17
• 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.
• Identification of OxyE as an Ancillary Oxygenase during Tetracycline Biosynthesis
  作者：Peng Wang、Wenjun Zhang、Jixun Zhan、Yi Tang

  DOI：10.1002/cbic.200900122

  日期：2009.6.15

  Ancillary oxygenase: OxyE is identified as a likely ancillary C‐4 hydroxylase used during oxytetracycline biosynthesis in Streptomyces rimosus. The synergistic actions of oxygenases OxyE and OxyL ensure complete oxidative tailoring and prevent irreversible shunt modifications of the biosynthetic intermediate.

  辅助加氧酶：OxyE被认为是在金黄色链霉菌中土霉素的生物合成过程中使用的一种可能的辅助C-4羟化酶。氧化酶OxyE和OxyL的协同作用可确保完全的氧化调节，并防止生物合成中间体的不可逆分流修饰。