特曲霉素A2 | 82277-62-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 并四苯
• 中文名称: 特曲霉素A2
• 英文名称: tetracenomycin A2
• 英文别名: methyl 10,12-dihydroxy-3,8-dimethoxy-1-methyl-6,11-dioxotetracene-2-carboxylate
• CAS: 82277-62-1
• 化学式: C₂₃H₁₈O₈
• 分子量: 422.391
• InChiKey: BXLGPMDGOMEFBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  特曲霉素A2 在 ElmG DL-dithiothreitol 、 三羟甲基氨基甲烷盐酸盐 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 二甲基亚砜 为溶剂， 以100%的产率得到特曲霉素C
  参考文献：
  名称：

  ElmGHIJ基因的克隆，测序和异源表达，涉及寡聚链霉菌Tü2353的聚酮化合物抗生素elloramycin的生物合成。

  摘要：

  Elloramycin A（1）属于萘并苯醌的小家族，其特征在于独特的高度羟基化的环己烯酮部分。先前已经分离了粘粒克隆16F4，其具有用于从橄榄链霉菌Tü2353生产1的基因。对来自16F4的3.2kb片段的DNA序列分析揭示了四个开放阅读框-elmGHIJ基因。ElmGHI基因在大肠杆菌或淡链霉菌中的异源表达，然后对ElmGHI蛋白进行生化表征，确定ElmG为四西松霉素B2加氧酶，ElmH为四西松霉素F1单加氧酶，ElmI为四西松霉素F1单加氧酶。这些结果为S中1的生物合成提供了直接的生化证据。

  DOI：

  10.1021/np010007+
• 作为产物：
  描述：

  methyl 6-deoxykermesate 在 盐酸 、 sodium tetrahydroborate 、 air 、 silver(l) oxide 作用下， 生成 特曲霉素A2
  参考文献：
  名称：

  Synthesis of tetracenomycins

  摘要：

  Tetracenomycins D, A2, B1 and B2 (2)-(5) have been synthesised for the first time, by an efficient, regioselective sequence based on cycloaddition methodology; the ambiguity that existed for tetracenomycins B1 and B2 has thereby been resolved in favour of structures (4a) and (5b) respectively.

  DOI：

  10.1016/s0040-4039(00)61155-3

文献信息

• Overproduction of the acyl carrier protein component of a type II polyketide synthase stimulates production of tetracenomycin biosynthetic intermediates in Stteptomyces glaucescens.
  作者：HEINRICH DECKER、RICHARD G. SUMMERS、C. RICHARD HUTCHINSON

  DOI：10.7164/antibiotics.47.54

  日期：——

  The development of microorganisms with improved antibiotic production is an important goal in the commercialization of new Pharmaceuticals or in lowering the cost of established drugs. We report a way to achieve this for biosynthetic intermediates of an antibiotic made by the polyketide pathway whose earliest steps involve a Type II multienzyme complex. Introduction of the tcmKLM β-ketoacyl: ACP synthase and acyl carrier protein (ACP) genes or just the tcmM ACP gene into the tetracenomycin (Tcm) C-producing Streptomyces glaucescens wild-type strain, or its tcmN or tcmO blocked mutants, on high copy vectors under the control of strong promoters caused a 2 to 30-fold overproduction of Tcm D3 and some other biosynthetic intermediates (or shunt products) and a 25 to 30% increase in Tcm C production relative to the control strains carrying the plasmid vector only. However, Tcm C production was not greater than that obtained with the vector-free wild-type strain. The unexpected effect of increased ACP on Tcm D3 production suggests that the level of this protein can influence either the activity or level of the three other components of the Tcm polyketide synthase.

  提高抗生素生产能力的微生物开发是新型药物商业化或降低现有药物成本的重要目标。我们报告了一种通过多肽途径生产抗生素生物合成中间体的途径，该途径的早期步骤涉及II型多酶复合物。将tcmKLM β-酮酰基：ACP合成酶和酰基载体蛋白（ACP）基因或仅将tcmM ACP基因引入四环素（Tcm）C生产链霉菌野生型菌株或其tcmN或tcmO阻断突变体，在高拷贝载体上，在强启动子的控制下，与仅携带质粒载体的对照菌株相比，Tcm D3和其他一些生物合成中间体（或分流产物）的产量提高了2至30倍，Tcm C的产量提高了25%至30%。然而，Tcm C的产量并不比无载体野生型菌株的产量高。ACP对Tcm D3产量增加的意外影响表明，这种蛋白质的水平会影响Tcm多�
• Triple Hydroxylation of Tetracenomycin A2 to Tetracenomycin C Involving Two Molecules of O₂ and One Molecule of H₂O
  作者：Elpidio R. Rafanan,、C. Richard Hutchinson、Ben Shen

  DOI：10.1021/ol0002267

  日期：2000.10.1

  The TcmG or ElmG oxygenase-catalyzed triple hydroxylation of tetracenomycin (Tcm) A2 to Tcm C proceeds via a novel monooxygenase-dioxygenase mechanism, deriving the 4- and 12a-OH groups of Tcm C from two molecules of O(2) and the 4a-OH group of Tcm C from a molecule of H(2)O. These results suggest a mechanistic analogy among TcmG, ElmG, and the bacterial and fungal hydroquinone epoxidizing dioxygenases, as well as the mammalian vitamin K-dependent gamma-glutamyl carboxylase.
• Crystallization and preliminary X-ray analysis of tetracenomycin A2 oxygenase: a flavoprotein hydroxylase involved in polyketide biosynthesis
  作者：John Beynon、Elpidio R. Rafanan、Ben Shen、Andrew J. Fisher

  DOI：10.1107/s0907444900012695

  日期：2000.12.1

  The tcm operon in Streptomyces glaucescens encodes a group of enzymes involved in the synthesis of the polyketide tetracenomycin (Tcm) C that exhibits both antitumor and antibiotic activities. Here, the crystallization and preliminary data characterization of the tcmG gene product, Tcm A2 oxygenase, which catalyzes the triple hydroxylation of Tcm A2 to form Tcm C, are reported. Tcm A2 oxygenase crystallizes in two different space groups, both with six monomers per asymmetric unit, resulting in large unit-cell parameters. Synchrotron data have been collected from both the hexagonal and tetragonal crystal forms to 4.5 and 4.2 Angstrom, respectively. The self-rotation function searches in both space groups suggest the monomers assemble into a complex with D-3 symmetry.
• Shen B.; Hutchinson C.R., J Biol Chem, 1994, 0021-9258, 30726-33
  作者：Shen B.、Hutchinson C.R.

  DOI：——

  日期：——