methylmalonyl CoA | 1264-45-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methylmalonyl CoA
• 英文别名: β-methylmalonyl-CoA；S-(2-carboxy-propionyl)-coenzyme-A；Methyl-malonyl-coenzym A；Methylmalonyl-coenzym A；9-{5-O-[{[(4-{[3-({2-[(2-Carboxypropanoyl)sulfanyl]ethyl}imino)-3-hydroxypropyl]imino}-3,4-dihydroxy-2,2-dimethylbutoxy)(hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl]-3-O-phosphonopentofuranosyl}-9H-purin-6-amine；3-[2-[3-[[4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethylsulfanyl]-2-methyl-3-oxopropanoic acid
• CAS: 1264-45-5；10251-08-8；73173-91-8；73173-92-9
• 化学式: C₂₅H₄₀N₇O₁₉P₃S
• 分子量: 867.615
• InChiKey: MZFOKIKEPGUZEN-RVTPZZGCSA-N

物化性质

• 密度：
  1.92±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.4
• 重原子数：
  55
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  426
• 氢给体数：
  10
• 氢受体数：
  24

反应信息

• 作为反应物：
  描述：

  methylmalonyl CoA 在 乙二胺四乙酸 、 recombinant Aloe arborescens octaketide synthase 作用下， 以 phosphate buffer 为溶剂， 反应 12.0h， 生成 6-ethyl-4-hydroxy-3,5-dimethyl-2-pyrone
  参考文献：
  名称：

  Enzymatic formation of an unnatural methylated triketide by plant type III polyketide synthases

  摘要：

  Octaketide synthase, a novel plant-specific type III polyketide synthase from Aloe arborescens, efficiently accepted (2RS)-methylmalonyl-CoA as a sole substrate to produce 6-ethyl-4-hydroxy-3,5-dimethyl-2-pyrone. On the other hand, a tetraketide-producing chalcone synthase from Scutellaria baicalensis and a diketide-producing benzalacetone synthase from Rheum palmatum also yielded the unnatural methylated C-9 triketide pyrone as a single product by sequential decarboxylative condensations of three molecules of (2RS)-methylmalonyl-CoA. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.10.012
• 作为产物：
  描述：

  甲基丙二酸 、 coenzyme A 在 malonyl-CoA synthetase from Rhizobium trifolii 、 5’-三磷酸腺苷 、 magnesium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 反应 3.0h， 生成 methylmalonyl CoA
  参考文献：
  名称：

  通过工程酰基辅酶A合成酶揭示了多特异性反式酰基转移酶机制

  摘要：

  聚酮化合物合酶通过增量剂单元和酰基硫酯的缩合来构建具有多种结构和生物活性的聚酮化合物。尽管越来越多的证据表明，聚酮化合物合酶可能在体外和体内都可以耐受非天然扩展剂由于缺乏合成多种酰基辅酶A增量剂单元的途径，旨在探索和利用聚酮化合物合酶特异性的研究被严格限制在仅少量的增量剂单元中。在这里，我们报告了混杂的丙二酰-CoA合成酶变体的构建，该变体可用于合成在C2位置取代的大范围的丙二酰-CoA扩展剂单元，其中一些包含用于化学选择性连接的手柄，在天然生物合成中未发现系统。我们通过探究几种反式的酰基辅酶A特异性突出了这些酶的效用。-酰基转移酶，导致对非天然延伸单元的多特异性的空前发现，其中几种在天然生物合成途径中未发现。这些结果表明，聚酮化合物的生物合成机制对非天然底物的耐受性可能比以前建立的更高，并且突变体合成酶是探测生物合成机制特异性的有价值的工具。我们的数据提出了利用这种滥交和实现聚酮化合物的区域选择性修饰的新的合成生物学策略。

  DOI：

  10.1021/cb3003489

文献信息

• Synthetic Chain Terminators Off-Load Intermediates from a Type I Polyketide Synthase
  作者：Manuela Tosin、Lorena Betancor、Elaine Stephens、W. M. Ariel Li、Jonathan B. Spencer、Peter F. Leadlay

  DOI：10.1002/cbic.200900772

  日期：2010.3.1

  To catch and off load: Intermediate species in type I modular polyketide biosynthesis were captured in vitro by small molecules that efficiently compete with the natural methylmalonyl extender units recruited for polyketide formation. The intermediates, which were directly off‐loaded from a whole polyketide synthase in action and characterised by LC‐HR‐ESI‐MS, are the first of their kind and prove

  赶上和卸载： I型模块化聚酮化合物生物合成中的中间物种是由小分子在体外捕获的，这些小分子可有效地与招募用于聚酮化合物形成的天然甲基丙二酸增量剂竞争。这些中间体是直接从整个聚酮化合物合酶上直接作用下来的，并通过LC-HR-ESI-MS进行了表征，是同类产品中的第一个，证明了小分子链终止剂是天然产物生物合成的便捷探针。
• Enzymatic Formation of Unnatural Novel Polyketides from Alternate Starter and Nonphysiological Extension Substrate by Chalcone Synthase
  作者：Ikuro Abe、Yusuke Takahashi、Weiwei Lou、Hiroshi Noguchi

  DOI：10.1021/ol0300165

  日期：2003.4.1

  [reaction: see text] In the chalcone synthase (CHS) enzyme reaction, both the starter molecule and the extension unit of the polyketide chain elongation reaction were simultaneously replaced with nonphysiological substrates. When incubated with benzoyl-CoA and methylmalonyl-CoA as substrates, recombinant CHS from Scutellaria baicalensis afforded an unnatural novel triketide, 4-hydroxy-3,5-dimethyl

  [反应：见正文]在查尔酮合酶（CHS）酶反应中，起始酮分子和聚酮化合物链延长反应的延伸单元同时被非生理性底物取代。当与苯甲酰辅酶A和甲基丙二酰辅酶A作为底物一起孵育时，黄S中的重组CHS提供了一种非天然的新型三酮化合物4-羟基-3,5-二甲基-6-苯基吡喃-2-酮以及四酮化合物4 -羟基-3,5-二甲基-6-（1-甲基-2-氧代-2-苯基-乙基）-吡喃-2-一。另一方面，该酶还接受己酰基-CoA和甲基丙二酰基-CoA作为底物，以产生非天然的新型三酮化合物4-羟基-3,5-二甲基-6-戊基-吡喃-2-酮。
• Characterization of AntB, a Promiscuous Acyltransferase Involved in Antimycin Biosynthesis
  作者：Moriah Sandy、Xuejun Zhu、Zhe Rui、Wenjun Zhang

  DOI：10.1021/ol4014365

  日期：2013.7.5

  The in vivo and in vitro characterization of AntB, a dedicated acyltransferase encoded in the antimycin biosynthetic gene cluster, which catalyzes the C-8 acyloxy formation is reported. It is demonstrated that AntB has broad substrate specificity toward both the acyl substrate and the acyl carrier and produces more antimycin analogues with varying C-8 acyloxy moieties.
• Synthesis and Biochemical Analysis of Complex Chain-Elongation Intermediates for Interrogation of Molecular Specificity in the Erythromycin and Pikromycin Polyketide Synthases
  作者：Jonathan D. Mortison、Jeffrey D. Kittendorf、David H. Sherman

  DOI：10.1021/ja9060596

  日期：2009.11.4

  The 6-deoxyerythronolide B synthase (DEBS) and pikromycin (Pik) polyketide synthase (PKS) are unique multifunctional enzyme systems that are responsible for the biosynthesis of the erythromycin and pikromycin 14-membered ring aglycones, respectively. Together, these natural product biosynthetic systems provide excellent platforms to examine the fundamental structural and catalytic elements that govern polyketide assembly, processing, and macrocyclization. In these studies, the native pentaketide intermediate for DEBS was synthesized and employed for in vitro chemoenzymatic synthesis of macrolactone products in engineered monomodules Ery5, Ery5-TE, and Ery6. A comparative analysis was performed with the corresponding Pik module 5 (PikAIII) and module 6 (PikAIV), dissecting key similarities and differences between these highly related PKSs. The data revealed that individual modules in the DEBS and Pik PKSs possess distinctive molecular selectivity profiles and suggest that substrate recognition has evolved unique characteristics in each system.
• Poly Specific <i>trans</i>-Acyltransferase Machinery Revealed <i>via</i> Engineered Acyl-CoA Synthetases
  作者：Irina Koryakina、John McArthur、Shan Randall、Matthew M. Draelos、Ewa M. Musiol、David C. Muddiman、Tilmann Weber、Gavin J. Williams

  DOI：10.1021/cb3003489

  日期：2013.1.18

  Polyketide synthases construct polyketides with diverse structures and biological activities via the condensation of extender units and acyl thioesters. Although a growing body of evidence suggests that polyketide synthases might be tolerant to non-natural extender units, in vitro and in vivo studies aimed at probing and utilizing polyketide synthase specificity are severely limited to only a small

  聚酮化合物合酶通过增量剂单元和酰基硫酯的缩合来构建具有多种结构和生物活性的聚酮化合物。尽管越来越多的证据表明，聚酮化合物合酶可能在体外和体内都可以耐受非天然扩展剂由于缺乏合成多种酰基辅酶A增量剂单元的途径，旨在探索和利用聚酮化合物合酶特异性的研究被严格限制在仅少量的增量剂单元中。在这里，我们报告了混杂的丙二酰-CoA合成酶变体的构建，该变体可用于合成在C2位置取代的大范围的丙二酰-CoA扩展剂单元，其中一些包含用于化学选择性连接的手柄，在天然生物合成中未发现系统。我们通过探究几种反式的酰基辅酶A特异性突出了这些酶的效用。-酰基转移酶，导致对非天然延伸单元的多特异性的空前发现，其中几种在天然生物合成途径中未发现。这些结果表明，聚酮化合物的生物合成机制对非天然底物的耐受性可能比以前建立的更高，并且突变体合成酶是探测生物合成机制特异性的有价值的工具。我们的数据提出了利用这种滥交和实现聚酮化合物的区域选择性修饰的新的合成生物学策略。