(3,5-Dichloro-2,4,6-trihydroxyphenyl)hexan-1-one(1-)

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3,5-Dichloro-2,4,6-trihydroxyphenyl)hexan-1-one(1-)
• 英文别名: 2,6-dichloro-4-hexanoyl-3,5-dihydroxyphenolate
• 化学式: C12H13Cl2O4-
• 分子量: 292.13
• InChiKey: WLWLDMLTAFSEDI-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3,5-Dichloro-2,4,6-trihydroxyphenyl)hexan-1-one(1-) 、 S-腺苷蛋氨酸 生成 1-(3,5-Dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one(1-) 、 氢(+1)阳离子 、 S-(5'-腺苷)-L-高半胱氨酸
  参考文献：
  名称：

  The Biosynthesis of Differentiation-Inducing Factor, a Chlorinated Signal Molecule Regulating DictyosteliumDevelopment

  摘要：

  Differentiation-inducing factor (DIF)-1 is a chlorinated alkyl phenone released by developing Dictyostelium amoebae, which induces them to differentiate into stalk cells, A biosynthetic pathway for DIF-1 is proposed from labeling, inhibitor, and enzymological experiments, Cells incorporate Cl-36(-) into DIF-1 during development, showing that the chlorine atoms originate from chloride ions; peak incorporation is at the first finger stage, DIF-1 synthesis can be blocked by cerulenin, a polyketide synthase inhibitor, suggesting that it is made from a polyketide, This is most likely the C-12 polyketide (2,4,6-trihydroxyphenyl)-1-hexan-1-one (THPH). Feeding experiments confirm that living cells can convert THPH to DIF-1, Conversion requires both chlorination and methylation of THPH, and enzymatic activities able to do this exist in cell lysates, The chlorinating activity, assayed using Cl-36(-), is stimulated by H2O2 and requires both soluble and particulate components, It is specific for THPH and does not use this compound after O-methylation. The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a K-m for dichloro-THPH of about 1.1 mu M, and strongly prefers this substrate to close analogues, Both chlorinating and methyltransferase activities increase in development in parallel with DIF-1 production, and both are greatly reduced in a mutant strain that makes little DIF-1, It is proposed that DIF-1 is made by the initial assembly of a C-12 polyketide skeleton, which is then chlorinated and methylated.

  DOI：

  10.1074/jbc.273.5.2669
• 作为产物：
  描述：

  chloro-THPH(1-) 、 氯离子 、 10-[(2S,3S,4R)-5-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2,3,4-trihydroxypentyl]-7,8-dimethyl-5H-benzo[g]pteridine-2,4-diolate 、 氧气 生成 (3,5-Dichloro-2,4,6-trihydroxyphenyl)hexan-1-one(1-) 、 FAD 、 水
  参考文献：
  名称：

  A flavin-dependent halogenase catalyzes the chlorination step in the biosynthesis of Dictyostelium differentiation-inducing factor 1

  摘要：

  诱导分化因子1（DIF-1）是一种由聚酮衍生的形态因子，在Dictyostelium discoideum的发育周期中促进茎细胞形成。先前的实验表明，生物合成途径通过对前体分子THPH的二氯化进行。但负责这一转化的酶尚未被表征。我们最近对原核黄酮依赖卤素酶的研究以及从已测序的Dd基因组中获得的见解，让我们找到了这一转化的候选基因。在这项工作中，我们提供了体内和体外证据，表明Dd中的chlA编码一种能够催化DIF-1生物合成中的两次氯化的黄酮依赖卤素酶。这些结果提供了一个关于真核氧依赖卤素酶的体外特征化，并展示了这种分子修饰策略在生物学中的广泛应用，尤其是在社会变形虫的分化程序中的参与。

  DOI：

  10.1073/pnas.1001681107

文献信息

• A flavin-dependent halogenase catalyzes the chlorination step in the biosynthesis of <i>Dictyostelium</i> differentiation-inducing factor 1
  作者：Christopher S. Neumann、Christopher T. Walsh、Robert R. Kay

  DOI：10.1073/pnas.1001681107

  日期：2010.3.30

  Differentiation-inducing factor 1 (DIF-1) is a polyketide-derived morphogen which drives stalk cell formation in the developmental cycle of Dictyostelium discoideum . Previous experiments demonstrated that the biosynthetic pathway proceeds via dichlorination of the precursor molecule THPH, but the enzyme responsible for this transformation has eluded characterization. Our recent studies on prokaryotic flavin-dependent halogenases and insights from the sequenced Dd genome led us to a candidate gene for this transformation. In this work, we present in vivo and in vitro evidence that chlA from Dd encodes a flavin-dependent halogenase capable of catalyzing both chlorinations in the biosynthesis of DIF-1. The results provide in vitro characterization of a eukaryotic oxygen-dependent halogenase and demonstrate a broad reach in biology for this molecular tailoring strategy, notably its involvement in the differentiation program of a social amoeba.

  诱导分化因子1（DIF-1）是一种由聚酮衍生的形态因子，在Dictyostelium discoideum的发育周期中促进茎细胞形成。先前的实验表明，生物合成途径通过对前体分子THPH的二氯化进行。但负责这一转化的酶尚未被表征。我们最近对原核黄酮依赖卤素酶的研究以及从已测序的Dd基因组中获得的见解，让我们找到了这一转化的候选基因。在这项工作中，我们提供了体内和体外证据，表明Dd中的chlA编码一种能够催化DIF-1生物合成中的两次氯化的黄酮依赖卤素酶。这些结果提供了一个关于真核氧依赖卤素酶的体外特征化，并展示了这种分子修饰策略在生物学中的广泛应用，尤其是在社会变形虫的分化程序中的参与。
• The Biosynthesis of Differentiation-Inducing Factor, a Chlorinated Signal Molecule Regulating DictyosteliumDevelopment
  作者：Robert R. Kay

  DOI：10.1074/jbc.273.5.2669

  日期：1998.1

  Differentiation-inducing factor (DIF)-1 is a chlorinated alkyl phenone released by developing Dictyostelium amoebae, which induces them to differentiate into stalk cells, A biosynthetic pathway for DIF-1 is proposed from labeling, inhibitor, and enzymological experiments, Cells incorporate Cl-36(-) into DIF-1 during development, showing that the chlorine atoms originate from chloride ions; peak incorporation is at the first finger stage, DIF-1 synthesis can be blocked by cerulenin, a polyketide synthase inhibitor, suggesting that it is made from a polyketide, This is most likely the C-12 polyketide (2,4,6-trihydroxyphenyl)-1-hexan-1-one (THPH). Feeding experiments confirm that living cells can convert THPH to DIF-1, Conversion requires both chlorination and methylation of THPH, and enzymatic activities able to do this exist in cell lysates, The chlorinating activity, assayed using Cl-36(-), is stimulated by H2O2 and requires both soluble and particulate components, It is specific for THPH and does not use this compound after O-methylation. The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a K-m for dichloro-THPH of about 1.1 mu M, and strongly prefers this substrate to close analogues, Both chlorinating and methyltransferase activities increase in development in parallel with DIF-1 production, and both are greatly reduced in a mutant strain that makes little DIF-1, It is proposed that DIF-1 is made by the initial assembly of a C-12 polyketide skeleton, which is then chlorinated and methylated.