dehydrorabelomycin | 30954-70-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 角环素
• 英文名称: dehydrorabelomycin
• 英文别名: 6-hydroxytetrangulol；1,6,8-trihydroxy-3-methylbenzo[a]anthracene-7,12-dione
• CAS: 30954-70-2
• 化学式: C₁₉H₁₂O₅
• 分子量: 320.301
• InChiKey: PQVIKROZFPIERS-UHFFFAOYSA-N

物化性质

• 沸点：
  609.8±50.0 °C(Predicted)
• 密度：
  1.564±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dehydrorabelomycin 在 glucose-6-phosphate dehydrogenase 、 D-葡萄糖-6-磷酸 、 GilM O-methyltransferase 、 GilMT O-methyltransferase 、 GilOII oxygenase 、 GilR oxido reductase 、 S-adenosylmethionine 、 还原型辅酶II(NADPH)四钠盐 、 腺嘌呤黄素 、 magnesium chloride 作用下， 以 水 为溶剂， 反应 8.0h， 以80%的产率得到defucogilvocarcin M
  参考文献：
  名称：

  Defucogilvocarcin M 的酶促全合成及其对 Gilvocarcin 生物合成的影响

  摘要：

  团队合作：Defucogilvocarcin M（1，见方案）是通过一锅法合成的，由乙酰辅酶A和丙二酰辅酶A通过15种酶的组合从乙酰辅酶A和丙二酰辅酶A中合成，并结合了从大肠杆菌中获得的15种酶以及gilvocarcin、jadomycin和ravidomycin生物合成途径。酶的混合物被系统地减少和改变，以进一步描绘 gilvocarcin 生物合成的复杂的聚酮化合物后步骤中的反应顺序。

  DOI：

  10.1002/anie.201105882
• 作为产物：
  描述：

  在 三氯化铝 、 palladium diacetate 、 乙硫醇 作用下， 以 乙腈 为溶剂， 反应 14.0h， 生成 dehydrorabelomycin
  参考文献：
  名称：

  A General Approach to Angucyclines: Synthesis of Hatomarubigin A, Rubiginone B2, Antibiotic X-1488E, 6-Hydroxytetrangulol, and Tetrangulol

  摘要：

  Hatomarubigin A was prepared in 41% yield in a single procedure from acyl naphthoquinone 15 and 5-methylcyclohexane-1,3-dione (16). The net reaction consists of Michael addition to an acyl quinone followed by intramolecular aldol condensation. Hatomarubigin A then served as a common intermediate in syntheses of the angucyclinone antibiotics rubiginone B2, antibiotic X-1488E, 6-hydroxy-tetrangulol, and tetrangulol. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00869-3

文献信息

• Production of Stealthin C Involves an S–N-Type Smiles Rearrangement
  作者：Peng Wang、Gloria J. Hong、Matthew R. Wilson、Emily P. Balskus

  DOI：10.1021/jacs.6b10586

  日期：2017.3.1

  monooxygenase AlpJ, can generate these metabolites from N-acetyl-l-cysteine and l-cysteine, respectively, and that the synthesis of stealthin C likely proceeds via a nonenzymatic S-N-type Smiles rearrangement. This unexpected route to stealthin C reveals a distinct approach to install aromatic amino groups in metabolites and raises questions about the intermediacy of this species in kinamycin production

  芳香族聚酮天然产物的运动霉素家族含有被重氮基团取代的非典型安古环素环系统。构建这两种结构特征所涉及的酶化学在很大程度上尚未被探索。在此，我们报告了 Seongomycin（该途径的一种分流产物）和 Stevethin C（一种建议的运动霉素生物合成前体）的体内和体外生产情况。我们证明，黄素依赖性单加氧酶 AlpJ 可以分别从 N-乙酰基-L-半胱氨酸和 L-半胱氨酸生成这些代谢物，并且隐形 C 的合成可能是通过非酶促 SN 型 Smiles 重排进行的。这种意想不到的隐形 C 途径揭示了一种在代谢物中安装芳香氨基的独特方法，并引发了关于该物种在运动霉素生产中的中间作用的问题。
• Characterization of JadH as an FAD- and NAD(P)H-Dependent Bifunctional Hydroxylase/Dehydrase in Jadomycin Biosynthesis
  作者：Yihua Chen、Keqiang Fan、Yongzhi He、Xinping Xu、Yanfeng Peng、Tingting Yu、Cuijuan Jia、Keqian Yang

  DOI：10.1002/cbic.201000178

  日期：——

  Biosynthesis of angucyclines: We characterized an accessory enzyme, JadH as a FAD and NAD(P)H‐dependent bifunctional hydroxylase/dehydrase involved in jadomycin biosynthesis by identifying its real product. Homologues of JadH have been found in all cloned angucycline biosynthetic clusters and were proposed to have similar functions as JadH.

  Angucyclines的生物合成：我们鉴定了辅助酶JadH作为FAD和依赖Jadomycin生物合成的NAD（P）H依赖性双功能羟化酶/脱水酶，方法是鉴定其真实产物。已在所有克隆的环霉素生物合成簇中发现了JadH的同系物，并被认为具有与JadH类似的功能。
• 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。
• Baeyer–Villiger C–C Bond Cleavage Reaction in Gilvocarcin and Jadomycin Biosynthesis
  作者：Nidhi Tibrewal、Pallab Pahari、Guojun Wang、Madan K. Kharel、Caleb Morris、Theresa Downey、Yanpeng Hou、Tim S. Bugni、Jürgen Rohr

  DOI：10.1021/ja3081154

  日期：2012.11.7

  GilOII has been unambiguously identified as the key enzyme performing the crucial C-C bond cleavage reaction responsible for the unique rearrangement of a benz[a]anthracene skeleton to the benzo[d]-naphthopyranone backbone typical of the gilvocarcin-type natural anticancer antibiotics. Further investigations of this enzyme led to the isolation of a hydroxyoxepinone intermediate, leading to important conclusions regarding the cleavage mechanism.
• Tailoring Enzymes Involved in the Biosynthesis of Angucyclines Contain Latent Context-Dependent Catalytic Activities
  作者：Pekka Patrikainen、Pauli Kallio、Keqiang Fan、Karel D. Klika、Khaled A. Shaaban、Pekka Mäntsälä、Jürgen Rohr、Keqian Yang、Jarmo Niemi、Mikko Metsä-Ketelä

  DOI：10.1016/j.chembiol.2012.04.010

  日期：2012.5

  Comparison of homologous angucycline modification enzymes from five closely related Streptomyces pathways (pga, cab, lad, urd, lan) allowed us to deduce the biosynthetic steps responsible for the three alternative outcomes: gaudimycin C, dehydrorabelomycin, and 11-deoxylandomycinone. The C-12b-hydroxylated urdamycin and gaudimycin metabolites appear to be the ancestral representatives from which landomycins and jadomysins have evolved as a result of functional divergence of the ketoreductase LanV and hydroxylase JadH, respectively. Specifically, LanV has acquired affinity for an earlier biosynthetic intermediate resulting in a switch in biosynthetic order and lack of hydroxyls at C-4a and C-12b, whereas in JadH, C-4a/C-12b dehydration has evolved into an independent secondary function replacing C-12b hydroxylation. Importantly, the study reveals that many of the modification enzymes carry several alternative, hidden, or ancestral catalytic functions, which are strictly dependent on the biosynthetic context.