dihydro-O-methylsterigmatocystin | 21793-91-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 杂色曲霉素
• 英文名称: dihydro-O-methylsterigmatocystin
• 英文别名: 8-O-Methyldihydrosterigmatocystin；(3S,7R)-11,15-dimethoxy-6,8,20-trioxapentacyclo[10.8.0.02,9.03,7.014,19]icosa-1,9,11,14(19),15,17-hexaen-13-one
• CAS: 21793-91-9；21885-65-4；24945-81-1
• 化学式: C₁₉H₁₆O₆
• 分子量: 340.332
• InChiKey: WSBZDTWHZJNGKQ-ZRNGKTOUSA-N

物化性质

• 沸点：
  556.1±50.0 °C(Predicted)
• 密度：
  1.377±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dihydro-O-methylsterigmatocystin 生成 [(3aR,8bS)-7-iodo-6-methoxy-1,2,3a,8b-tetrahydrofuro[2,3-b][1]benzofuran-8-yl] 2,6-dimethoxybenzoate
  参考文献：
  名称：

  HORNE, STEPHEN;RODRIGO, RUSSELL, J. ORG. CHEM., 55,(1990) N5, C. 4520-4522

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(2-二甲胺乙基)-5-甲基-吡唑-3-基胺 在 吡啶 、 氢氧化钾 、 正丁基锂 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 为溶剂， 反应 2.0h， 生成 dihydro-O-methylsterigmatocystin
  参考文献：
  名称：

  A complex induced proximity effect in the anionic Fries rearrangement of o-iodophenyl benzoates: synthesis of dihydro-O-methylsterigmatocystin and other xanthones

  摘要：

  DOI：

  10.1021/jo00302a011

文献信息

• Identification of O-methylsterigmatocystin as an aflatoxin B1 and G1 precursor in Aspergillus parasiticus
  作者：D Bhatnagar、S P McCormick、L S Lee、R A Hill

  DOI：10.1128/aem.53.5.1028-1033.1987

  日期：1987.5

  G1 were produced; 10 nmol of OMST produced 7.8 nmol of B1 and 1.0 nmol of G1, while 10 nmol of ST produced 6.4 nmol of B1 and 0.6 nmol of G1. A time course study of aflatoxin synthesis in ST feeding experiments with AVN-1 revealed that OMST is synthesized by the mold during the onset of aflatoxin synthesis. The total amount of aflatoxins recovered from OMST feeding experiments was higher than from

  分离的寄生曲霉CP461（SRRC 2043）没有产生可检出的黄曲霉毒素，但积累了O-甲基甾体藻毒素（OMST）。当在低糖培养基中将葡萄球菌毒素（ST）喂入该分离株时，OMST的积累增加，而没有黄曲霉毒素的合成。当将放射性标记的[14C] OMST喂入产寄生虫的非黄曲霉毒素，非ST-和非OMST突变体AVN-​​1（SRRC 163）的静息菌丝体时，用14C标记的黄曲霉毒素B1和G1产生 10nmol OMST产生7.8nmol B1和1.0nmol G1，而10nmol ST产生6.4nmol B1和0.6nmol G1。在AVN-1的ST饲喂实验中对黄曲霉毒素合成的时程研究表明，OMST是在黄曲霉毒素合成开始时由霉菌合成的。从OMST饲喂实验中回收的黄曲霉毒素总量高于将ST饲喂至静息菌丝体的实验。这些结果表明，OMST是黄曲霉毒素和黄曲霉毒素B1和G1之间黄曲霉毒素生物合成途径中的真正
• Characterization of the Critical Amino Acids of an <i>Aspergillus parasiticus</i> Cytochrome P-450 Monooxygenase Encoded by <i>ordA</i> That Is Involved in the Biosynthesis of Aflatoxins B ₁ , G ₁ , B ₂ , and G ₂
  作者：Jiujiang Yu、Perng-Kuang Chang、Kenneth C. Ehrlich、Jeffrey W. Cary、Beverly Montalbano、John M. Dyer、Deepak Bhatnagar、Thomas E. Cleveland

  DOI：10.1128/aem.64.12.4834-4841.1998

  日期：1998.12

  Complementation of A. parasiticus SRRC 2043, an OMST-accumulating strain, with the ordA gene restored the ability to produce aflatoxins B1, G1, B2, and G2. The ordA gene placed under the control of the GAL1 promoter converted exogenously supplied OMST to aflatoxin B1 in Saccharomyces cerevisiae. In contrast, the ordA gene homolog in A. parasiticus SRRC 2043, ordA1, was not able to carry out the same conversion

  O-甲基硬壳藻毒素（OMST）和二氢-O-甲基硬壳藻毒素向黄曲霉毒素B1，G1，B2和G2的转化需要细胞色素P-450类型的氧化还原酶活性。ordA是与omtA基因相邻的基因，通过在寄生曲霉中的染色体行走在黄曲霉毒素生物合成途径基因簇中鉴定出。ordA基因是黄曲霉ord1基因的同源物，它与OMST转化为黄曲霉毒素B1有关。寄生虫曲霉SRRC 2043（一种OMST积累菌株）与ordA基因的互补恢复了生产黄曲霉毒素B1，G1，B2和G2的能力。置于GAL1启动子控制下的ordA基因在酿酒酵母中转化成外源性的OMST，转化为黄曲霉毒素B1。相反，寄生寄生曲霉SRRC 2043中的ordA基因同源物ordA1 在酵母系统中无法进行相同的转化 序列分析显示ordA1基因具有三个点突变，导致三个氨基酸变化（His-400-> Leu-400，Ala-143-> Ser-143和Ile-528-> Tyr-528）
• Function of Native OmtA In Vivo and Expression and Distribution of This Protein in Colonies of <i>Aspergillus parasiticus</i>
  作者：Li-Wei Lee、Ching-Hsun Chiou、John E. Linz

  DOI：10.1128/aem.68.11.5718-5727.2002

  日期：2002.11

  The activities of two enzymes, a 168-kDa protein and a 40-kDa protein, OmtA, purified from the filamentous fungus Aspergillus parasiticus were reported to convert the aflatoxin pathway intermediate sterigmatocystin to O- methylsterigmatocystin in vitro. Our initial goal was to determine if OmtA is necessary and sufficient to catalyze this reaction in vivo and if this reaction is necessary for aflatoxin synthesis. We generated A. parasiticus omtA -null mutant LW1432 and a maltose binding protein-OmtA fusion protein expressed in Escherichia coli . Enzyme activity analysis of OmtA fusion protein in vitro confirmed the reported catalytic function of OmtA. Feeding studies conducted with LW1432 demonstrated a critical role for OmtA, and the reaction catalyzed by this enzyme in aflatoxin synthesis in vivo. Because of a close regulatory link between aflatoxin synthesis and asexual sporulation (conidiation), we hypothesized a spatial and temporal association between OmtA expression and conidiospore development. We developed a novel time-dependent colony fractionation protocol to analyze the accumulation and distribution of OmtA in fungal colonies grown on a solid medium that supports both toxin synthesis and conidiation. OmtA-specific polyclonal antibodies were purified by affinity chromatography using an LW1432 protein extract. OmtA was not detected in 24-h-old colonies but was detected in 48-h-old colonies using Western blot analysis; the protein accumulated in all fractions of a 72-h-old colony, including cells (0 to 24 h) in which little conidiophore development was observed. OmtA in older fractions of the colony (24 to 72 h) was partly degraded. Fluorescence-based immunohistochemical analysis conducted on thin sections of paraffin-embedded fungal cells from time-fractionated fungal colonies demonstrated that OmtA is evenly distributed among different cell types and is not concentrated in conidiophores. These data suggest that OmtA is present in newly formed fungal tissue and then is proteolytically cleaved as cells in that section of the colony age.

  摘要 从丝状真菌中纯化的两种酶的活性，一种是168-kDa蛋白，另一种是40-kDa蛋白OmtA。 寄生曲霉 将黄曲霉毒素途径中间体固形麦角甾醇转化为 O- 甲基甾体胱氨酸。我们最初的目标是确定 OmtA 是否是在体内催化这一反应的必要和充分条件，以及这一反应是否是黄曲霉毒素合成所必需的。我们生成了 寄生虫 OmtA -缺失突变体 LW1432 和在大肠杆菌中表达的麦芽糖结合蛋白-OmtA 融合蛋白。 大肠杆菌 .对 OmtA 融合蛋白的体外酶活性分析证实了所报道的 OmtA 的催化功能。用 LW1432 进行的饲养研究表明，OmtA 及其催化的反应在黄曲霉毒素的体内合成中起着关键作用。由于黄曲霉毒素的合成与无性孢子（分生孢子）之间存在密切的调控联系，我们假设 OmtA 的表达与分生孢子的发育之间存在时空联系。我们开发了一种新型的时间依赖性菌落分馏方案，用于分析在同时支持毒素合成和分生孢子的固体培养基上生长的真菌菌落中 OmtA 的积累和分布情况。使用 LW1432 蛋白提取物通过亲和层析纯化了 OmtA 特异性多克隆抗体。在生长 24 小时的菌落中未检测到 OmtA，但在生长 48 小时的菌落中通过 Western 印迹分析检测到了 OmtA；在生长 72 小时的菌落的所有馏分中都积累了该蛋白，包括几乎未观察到分生孢子发育的细胞（0 至 24 小时）。菌落较老部分（24 至 72 小时）中的 OmtA 部分降解。对按时间分馏的真菌菌落中石蜡包埋的真菌细胞薄片进行的荧光免疫组化分析表明，OmtA 均匀地分布在不同类型的细胞中，并不集中在分生孢子器中。这些数据表明，OmtA 存在于新形成的真菌组织中，然后随着菌落该部分细胞的老化而被蛋白水解。
• Cloning and characterization of a cDNA from Aspergillus parasiticus encoding an O-methyltransferase involved in aflatoxin biosynthesis
  作者：J Yu、J W Cary、D Bhatnagar、T E Cleveland、N P Keller、F S Chu

  DOI：10.1128/aem.59.11.3564-3571.1993

  日期：1993.11

  Aflatoxins are polyketide-derived secondary metabolites produced by the fungi Aspergillus flavus and Aspergillus parasiticus. Among the catalytic steps in the aflatoxin biosynthetic pathway, the conversion of sterigmatocystin to O-methylsterigmatocystin and the conversion of dihydrosterigmatocystin to dihydro-O-methylsterigmatocystin are catalyzed by an S-adenosylmethionine-dependent O-methyltransferase. A cDNA library was constructed by using RNA isolated from a 24-h-old culture of wild-type A. parasiticus SRRC 143 and was screened by using polyclonal antiserum raised against a purified 40-kDa O-methyltransferase protein. A clone that harbored a full-length cDNA insert (1,460 bp) containing the 1,254-bp coding region of the gene omt-1 was identified by the antiserum and isolated. The complete cDNA sequence was determined, and the corresponding 418-amino-acid sequence of the native enzyme with a molecular weight of 46,000 was deduced. This 46-kDa native enzyme has a leader sequence of 41 amino acids, and the mature form of the enzyme apparently consists of 377 amino acids and has a molecular weight of 42,000. Direct sequencing of the purified mature enzyme from A. parasiticus SRRC 163 showed that 19 of 22 amino acid residues were identical to the amino acid residues in an internal region of the deduced amino acid sequence of the mature protein. The 1,460-bp omt-1 cDNA was cloned into an Escherichia coli expression system; a Western blot (immunoblot) analysis of crude extracts from this expression system revealed a 51-kDa fusion protein (fused with a 5-kDa beta-galactosidase N-terminal fragment).(ABSTRACT TRUNCATED AT 250 WORDS)

  黄曲霉菌和寄生曲霉菌产生的多酮衍生的次生代谢产物称为黄曲霉毒素。在黄曲霉毒素生物合成途径中的催化步骤中，将立青霉素转化为O-甲基立青霉素和将二氢立青霉素转化为二氢-O-甲基立青霉素均由S-腺苷甲硫氨酸依赖的O-甲基转移酶催化。使用从野生型寄生曲霉菌SRRC 143的24小时培养物中分离的RNA构建了一个cDNA文库，并使用针对纯化的40 kDa O-甲基转移酶蛋白制备的多克隆抗血清进行筛选。通过抗血清鉴定并分离出含有全长cDNA插入物（1,460 bp）的克隆，其中包含基因omt-1的1,254 bp编码区域。确定了完整的cDNA序列，并推导出具有分子量46,000的天然酶的相应的418个氨基酸序列。这种46 kDa的天然酶具有41个氨基酸的信号序列，成熟形式的酶显然由377个氨基酸组成，分子量为42,000。从寄生曲霉菌SRRC 163纯化的成熟酶进行直接测序，显示22个氨基酸残基中有19个与成熟蛋白的推导氨基酸序列的内部区域中的氨基酸残基相同。将1,460 bp omt-1 cDNA克隆到大肠杆菌表达系统中，对来自该表达系统的粗提取物进行Western blot（免疫印迹）分析，显示出一个51 kDa的融合蛋白（与5 kDa的β-半乳糖苷酶N-末端片段融合）。
• HORNE, STEPHEN;RODRIGO, RUSSELL, J. ORG. CHEM., 55,(1990) N5, C. 4520-4522
  作者：HORNE, STEPHEN、RODRIGO, RUSSELL

  DOI：——

  日期：——