gaudimycin C | 1012859-41-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: gaudimycin C
• 英文别名: (4aR,6S,12bS)-4a,6,8,12b-tetrahydroxy-3-methyl-5,6-dihydro-4H-benzo[a]anthracene-1,7,12-trione
• CAS: 1012859-41-4
• 化学式: C₁₉H₁₆O₇
• 分子量: 356.332
• InChiKey: XKRMMVFULPCHPV-SYURPWHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  26
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  gaudimycin C 在 LanV 、 NADPH-dependent flavoprotein hydroxylase LanE 、 还原型辅酶II(NADPH)四钠盐 作用下， 生成 11-deoxylandomycinone
  参考文献：
  名称：

  Tailoring Enzymes Involved in the Biosynthesis of Angucyclines Contain Latent Context-Dependent Catalytic Activities

  摘要：

  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.

  DOI：

  10.1016/j.chembiol.2012.04.010
• 作为产物：
  描述：

  prejadomycin 在 CabV 、 PgaE 、 氧气 、 还原型辅酶II(NADPH)四钠盐 作用下， 生成 gaudimycin C
  参考文献：
  名称：

  Angucycline C-6酮还原酶LanV参与Landomycin生物合成的结构和功能分析

  摘要：

  Angucyclines是生物围绕公共苯并〔构造活性天然产物一]蒽醌碳帧。安古环素生物合成中的一个关键分支点是C-6的酮还原，这导致了兰霉素和乌达霉素/高迪霉素的立体化学相反。在这里，我们介绍了来自蓝链霉菌S136的LanV的1.65Å分辨率晶体结构，该晶体结构负责6 R土地霉素的立体化学。该酶显示出短链醇脱氢酶/还原酶的常见结构折叠，并含有结合的烟酰胺腺嘌呤二核苷酸磷酸。在2.0Å分辨率下测定与11-脱氧山霉素的配合物中LanV的结构表明，底物结合不会引起大的构象变化，并且底物识别主要通过疏水相互作用发生。对三元络合物的电子密度图的分析表明，催化反应最有可能在晶体中向后进行，因为数据最适合于在C-6处带有羰基的化合物。在配体和保守的Tyr160残基之间非典型地确定了配位的水分子，通过定点诱变证实这对于催化活性至关重要。可以根据晶体结构识别Ser147，Tyr160和Lys164的催化三联

  DOI：

  10.1021/bi400712q

文献信息

• Flavoprotein Hydroxylase PgaE Catalyzes Two Consecutive Oxygen-Dependent Tailoring Reactions in Angucycline Biosynthesis
  作者：Pauli Kallio、Pekka Patrikainen、Jukka-Pekka Suomela、Pekka Mäntsälä、Mikko Metsä-Ketelä、Jarmo Niemi

  DOI：10.1021/bi200600k

  日期：2011.6.21

  A simplified model system composed of a NADPH-dependent flavoprotein hydroxylase PgaE and a short-chain alcohol dehydrogenase/reductase (SDR) CabV was used to dissect a multistep angucycline modification redox cascade into several subreactions in vitro. We demonstrate that the two enzymes are sufficient for the conversion of angucycline substrate 2,3-dehydro-UWM6 to gaudimycin C. The flavoenzyme PgaE

  由NADPH依赖性黄素羟化酶PgaE和短链醇脱氢酶/还原酶（SDR）CabV组成的简化模型系统用于在体外将多步环磷酰胺修饰氧化还原级联分解为几个亚反应。我们证明这两种酶足以将安古环素底物2,3-脱氢-UWM6转化为高迪霉素C。黄酮酶PgaE被证明负责两个连续的NADPH-和O 2-依赖性反应，与高迪霉素C中C-12和C-12b处的酶催化的氧原子掺入一致。这两个反应没有明显重叠，并且仅在原始底物2,3-之后才开始第二个催化循环脱氢-UWM6几乎耗尽。这使我们能够在限制的NADPH浓度下分离出第一个反应的产物，并能够研究分离出的反应的定性和动力学性质。解剖反应级联反应还使我们能够确定SDR还原酶CabV催化了最终的生物合成步骤，该步骤与第二个PgaE反应紧密相关。在没有CabV的情况下，完整的PgaE反应始终会导致产物降解，而在存在CabV的情况下，反应会产生最终产物高迪霉素C。结果表明，需要
• 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.