premithramycin B - lactone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: premithramycin B - lactone
• 英文别名: premithramycin B lactone；(3S,8S,9S)-6-acetyl-3-[(2S,4R,5R,6R)-4-[(2S,4R,5S,6R)-4-[(2S,4S,5R,6R)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-15-[(2S,4R,5R,6R)-4-[(2S,4R,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-7,17,19-trihydroxy-8-methoxy-16-methyl-5-oxatetracyclo[9.8.0.03,9.013,18]nonadeca-1(11),6,12,14,16,18-hexaene-2,4-dione
• 化学式: C₅₃H₇₂O₂₅
• 分子量: 1109.14
• InChiKey: BWNNJKJJQAJRNH-ZGFWTYNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  78
• 可旋转键数：
  12
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  364
• 氢给体数：
  10
• 氢受体数：
  25

反应信息

• 作为反应物：
  描述：

  premithramycin B - lactone 在 水 作用下， 生成 mithramycin DK
  参考文献：
  名称：

  Molecular Insight into Substrate Recognition and Catalysis of Baeyer–Villiger Monooxygenase MtmOIV, the Key Frame-Modifying Enzyme in the Biosynthesis of Anticancer Agent Mithramycin

  摘要：

  Baeyer-Villiger monooxygenases (BVMOs) have been shown to play key roles for the biosynthesis of important natural products. MtmOIV, a homodimeric FAD- and NADPH-dependent BVMO, catalyzes the key frame-modifying steps of the mithramycin biosynthetic pathway, including an oxidative C-C bond cleavage, by converting its natural substrate premithramycin B into mithramycin DK, the immediate precursor of mithramycin. The drastically improved protein structure of MtmOIV along with the high-resolution structure of MtmOIV in complex with its natural substrate premithramycin B are reported here, revealing previously undetected key residues that are important for substrate recognition and catalysis. Kinetic analyses of selected mutants allowed us to probe the substrate binding pocket of MtmOIV and also to discover the putative NADPH binding site. This is the first substrate-bound structure of MtmOIV providing new insights into substrate recognition and catalysis, which paves the way for the future design of a tailored enzyme for the chemo-enzymatic preparation of novel mithramycin analogues.

  DOI：

  10.1021/cb400399b
• 作为产物：
  描述：

  premithramycin B 在 Baeyer−Villiger monooxygenase MtmOIV 作用下， 生成 premithramycin B - lactone
  参考文献：
  名称：

  Molecular Insight into Substrate Recognition and Catalysis of Baeyer–Villiger Monooxygenase MtmOIV, the Key Frame-Modifying Enzyme in the Biosynthesis of Anticancer Agent Mithramycin

  摘要：

  Baeyer-Villiger monooxygenases (BVMOs) have been shown to play key roles for the biosynthesis of important natural products. MtmOIV, a homodimeric FAD- and NADPH-dependent BVMO, catalyzes the key frame-modifying steps of the mithramycin biosynthetic pathway, including an oxidative C-C bond cleavage, by converting its natural substrate premithramycin B into mithramycin DK, the immediate precursor of mithramycin. The drastically improved protein structure of MtmOIV along with the high-resolution structure of MtmOIV in complex with its natural substrate premithramycin B are reported here, revealing previously undetected key residues that are important for substrate recognition and catalysis. Kinetic analyses of selected mutants allowed us to probe the substrate binding pocket of MtmOIV and also to discover the putative NADPH binding site. This is the first substrate-bound structure of MtmOIV providing new insights into substrate recognition and catalysis, which paves the way for the future design of a tailored enzyme for the chemo-enzymatic preparation of novel mithramycin analogues.

  DOI：

  10.1021/cb400399b

文献信息

• Characterization of Kinetics and Products of the Baeyer−Villiger Oxygenase MtmOIV, The Key Enzyme of the Biosynthetic Pathway toward the Natural Product Anticancer Drug Mithramycin from <i>Streptomyces </i><i>a</i><i>rgillaceus</i>
  作者：Miranda Gibson、Mohammad Nur-e-alam、Fredilyn Lipata、Marcos A. Oliveira、Jürgen Rohr

  DOI：10.1021/ja055750t

  日期：2005.12.1

  MtmOIV, the key oxygenase of the mithramycin biosynthetic pathway in Streptomyces argillaceus, was proven to act initially as Baeyer-Villiger monooxygenase, but may also catalyze various follow-up reaction steps. The reaction of the overexpressed pure His6-tagged enzyme with its substrate premithramycin B was studied. Various intermediates and products were isolated and physicochemically characterized, several of them being previously unknown compounds. This is the first example in which a bacterial enzyme was unequivocally proven to act as Baeyer-Villigerase with its natural substrate, that is, in its natural context.