prejadomycin

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: prejadomycin
• 英文别名: (4aR,12bR)-4a,7,8-trihydroxy-3-methyl-5,12b-dihydro-4H-benzo[a]anthracene-1,6-dione
• 化学式: C₁₉H₁₆O₅
• 分子量: 324.333
• InChiKey: DAZPSZLIQWNPOM-PKOBYXMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 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：

  prejadomycin 在 glucose-6-phosphate dehydrogenase 、 D-葡萄糖-6-磷酸 、 GilM O-methyltransferase 、 GilMT O-methyltransferase 、 GilOI oxygenase 、 GilOII oxygenase 、 JadD type II polyketide synthase 、 JadF oxygenase 、 还原型辅酶II(NADPH)四钠盐 、 magnesium chloride 作用下， 以 水 为溶剂， 生成 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：

  angucyclinone UWM6 在 JadF 作用下， 生成 prejadomycin
  参考文献：
  名称：

  JadH在Jadomycin生物合成中作为FAD和NAD（P）H依赖性双功能羟化酶/脱水酶的特征

  摘要：

  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。

  DOI：

  10.1002/cbic.201000178

文献信息

• 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.
• Structure-Based Engineering of Angucyclinone 6-Ketoreductases
  作者：Pekka Patrikainen、Laila Niiranen、Keshav Thapa、Pasi Paananen、Petri Tähtinen、Pekka Mäntsälä、Jarmo Niemi、Mikko Metsä-Ketelä

  DOI：10.1016/j.chembiol.2014.07.017

  日期：2014.10

  Angucyclines are tetracyclic polyketides produced by Streptomyces bacteria that exhibit notable biological activities. The great diversity of angucyclinones is generated in tailoring reactions, which modify the common benz[a] anthraquinone carbon skeleton. In particular, the opposite stereochemistry of landomycins and urdamycins/gaudimycins at C-6 is generated by the short-chain alcohol dehydrogenases/reductases LanV and UrdMred/CabV, respectively. Here we present crystal structures of LanV and UrdMred in complex with NADP(+) and the product analog rabelomycin, which enabled us to identify four regions associated with the functional differentiation. The structural analysis was confirmed in chimeragenesis experiments focusing on these regions adjacent to the active site cavity, which led to reversal of the activities of LanV and CabV. The results surprisingly indicated that the conformation of the substrate and the stereochemical outcome of 6-ketoreduction appear to be intimately linked.