4-coumaroyl coenzyme A | 30802-00-7

• 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: 4-coumaroyl coenzyme A
• 英文别名: p-coumaroyl-coenzyme A；4-coumaroyl-CoA；p-coumaroyl-CoA；4-hydroxycinnamyl-CoA；S-[2-[3-[[(2R)-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]ethyl] 3-(4-hydroxyphenyl)prop-2-enethioate
• CAS: 30802-00-7
• 化学式: C₃₀H₄₂N₇O₁₈P₃S
• 分子量: 913.687
• InChiKey: DMZOKBALNZWDKI-FUEUKBNZSA-N

物化性质

• 密度：
  1.80±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.9
• 重原子数：
  59
• 可旋转键数：
  22
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  409
• 氢给体数：
  10
• 氢受体数：
  23

反应信息

• 作为反应物：
  描述：

  4-coumaroyl coenzyme A 在 <2-14C>malonyl-CoA 作用下， 生成 4-香豆酸
  参考文献：
  名称：

  Cloning and Structure-Function Analyses of Quinolone- and Acridone-producing Novel Type III Polyketide Synthases from Citrus microcarpa

  摘要：

  Two novel type III polyketide synthases, quinolone synthase (QNS) and acridone synthase (ACS), were cloned from Citrus microcarpa (Rutaceae). The deduced amino acid sequence of C. microcarpa QNS is unique, and it shared only 56-60% identities with C. microcarpa ACS, Medicago sativa chalcone synthase (CHS), and the previously reported Aegle marmelos QNS. In contrast to the quinolone- and acridone-producing A. marmelos QNS, C. microcarpa QNS produces 4-hydroxy-N-methylquinolone as the single product by the one-step condensation of N-methylanthraniloyl-CoA and malonyl-CoA. However, C. microcarpa ACS shows broad substrate specificities and produces not only acridone and quinolone but also chalcone, benzophenone, and phloroglucinol from 4-coumaroyl-CoA, benzoyl-CoA, and hexanoyl-CoA, respectively. Furthermore, the x-ray crystal structures of C. microcarpa QNS and ACS, solved at 2.47- and 2.35- resolutions, respectively, revealed wide active site entrances in both enzymes. The wide active site entrances thus provide sufficient space to facilitate the binding of the bulky N-methylanthraniloyl-CoA within the catalytic centers. However, the active site cavity volume of C. microcarpa ACS (760 (3)) is almost as large as that of M. sativa CHS (750 (3)), and ACS produces acridone by employing an active site cavity and catalytic machinery similar to those of CHS. In contrast, the cavity of C. microcarpa QNS (290 (3)) is significantly smaller, which makes this enzyme produce the diketide quinolone. These results as well as mutagenesis analyses provided the first structural bases for the anthranilate-derived production of the quinolone and acridone alkaloid by type III polyketide synthases.

  DOI：

  10.1074/jbc.m113.493155
• 作为产物：
  描述：

  对羟基肉桂酸 在 cyanobacterin long-chain acyl-coenzyme A synthetase 作用下， 生成 4-coumaroyl coenzyme A
  参考文献：
  名称：

  蓝细菌素的生物合成，呋喃内酯核心结构组装的范例

  摘要：

  γ-丁内酯基序存在于许多天然信号分子和其他特殊代谢物中。一个突出的例子是强效水生植物毒素蓝藻素，它具有高度功能化的 γ-丁内酯核心结构。几十年来，组装蓝藻素和结构相关的天然产物（本文称为呋喃内酯）的酶机制一直难以捉摸。在这里，我们阐明了呋喃内酯组装的生物合成过程。通过靶向生物信息学筛选鉴定蓝藻素生物合成基因簇，并通过大肠杆菌中的异源表达进行验证. 重组关键酶在体内和体外的完整功能评估，单独和协同，提供了对流线型 C-C 键形成级联的深入机制洞察，该级联涉及在氨基酸前体看似不反应的 Cα 位置安装相容的反应性. 我们的工作扩展了 γ- 丁内酯形成的生物合成和生物催化工具箱，为呋喃内酯生物合成提供了一个通用范例，并为其靶向发现、生物合成工程和酶促合成奠定了基础。

  DOI：

  10.1038/s41589-022-01013-7

文献信息

• A versatile biosynthetic approach to amide bond formation
  作者：Helena K. Philpott、Pamela J. Thomas、David Tew、Doug E. Fuerst、Sarah L. Lovelock

  DOI：10.1039/c8gc01697f

  日期：——

  The development of versatile and sustainable catalytic strategies for amide bond formation is a major objective for the pharmaceutical sector and the wider chemical industry. Herein, we report a biocatalytic approach to amide synthesis which exploits the diversity of Nature's amide bond forming enzymes, N-acyltransferases (NATs) and CoA ligases (CLs). By selecting combinations of NATs and CLs with

  通用和可持续的酰胺键形成催化策略的开发是制药行业和更广泛的化学工业的主要目标。在这里，我们报告了一种酰胺合成的生物催化方法，该方法利用了自然界中形成酰胺键的酶，N-酰基转移酶（NAT）和CoA连接酶（CL）的多样性。通过选择具有所需底物特征的NAT和CL的组合，可以以可预测的方式构建非天然的生物催化途径，以允许使用化学计量比的羧酸和胺偶联伙伴以高收率获得结构多样的仲和叔酰胺。可以使用分离的酶在体外或体内进行转化反应仅依赖于细胞产生的辅因子。这些全细胞系统的实用性通过Losmapimod的关键中间体（GW856553X）的制备规模合成得到展示，Losmapimod是一种选择性的p38促分裂原活化蛋白激酶抑制剂。
• Establishing a Toolkit for Precursor-Directed Polyketide Biosynthesis: Exploring Substrate Promiscuities of Acid-CoA Ligases
  作者：Maybelle Kho Go、Jeng Yeong Chow、Vivian Wing Ngar Cheung、Yan Ping Lim、Wen Shan Yew

  DOI：10.1021/bi300425j

  日期：2012.6.5

  biosynthesized from acyl-CoA precursors by polyketide synthases. One of the limitations to combinatorial biosynthesis of polyketides has been the lack of a toolkit that describes the means of delivering novel acyl-CoA precursors necessary for polyketide biosynthesis. Using five acid-CoA ligases obtained from various plants and microorganisms, we biosynthesized an initial library of 79 acyl-CoA thioesters by screening

  聚酮化合物是化学上多样化且具有医学上重要意义的生物化学物质，它们是通过聚酮化合物合酶从酰基辅酶A前体生物合成的。聚酮化合物的组合生物合成的局限性之一是缺少工具包，该工具包描述了递送聚酮化合物生物合成所必需的新型酰基-CoA前体的方法。使用从各种植物和微生物中获得的5种酸性CoA连接酶，我们通过针对123种羧酸的文库筛选每种酸性CoA连接酶，生物合成了79种酰基CoA硫酯的初始文库。酰基-CoA硫酯库包括肉桂基-CoA，3-苯基丙酰基-CoA，苯甲酰基-CoA，苯乙酰基-CoA，丙二酰-CoA，饱和和不饱和脂族CoA硫酯和双环芳族CoA硫酯的衍生物。在我们对新型酰基辅酶A前体的生物合成路线的搜索中，我们发现了两种以前未报道过的丙二酰辅酶A衍生物（3-硫代苯丙氨酰辅酶A和苯基丙二酰辅酶A），无法通过规范的丙二酰辅酶A合成酶生产。该报告强调了确定常规底物池之外底物混杂的实用性和重要性，并描述了建
• Cloning and Functional Characterization of Two 4-Coumarate: CoA Ligase Genes from Selaginella moellendorffii
  作者：Xin-Yan Liu、Ping-Ping Wang、Yi-Feng Wu、Ai-Xia Cheng、Hong-Xiang Lou

  DOI：10.3390/molecules23030595

  日期：——

  extensively characterized in other vascular plants, little is known of their functions in Selaginella. Here, we isolated two 4CL genes (Sm4CL1 and Sm4CL2) from Selaginella moellendorffii. Based on the enzymatic activities of the recombinant proteins, both of these genes encoded bona fide 4CLs. The 4CL isoforms in S. moellendorffii have different activities: Sm4CL2 was more active than Sm4CL1. The enzymatic properties

  卷柏是现存的苔藓双生植物属，代表了古代的气管植物谱系。重要的进化状态使其成为研究维管植物代谢进化的宝贵资源。4-香豆酸酯：CoA连接酶（4CL）是关键酶，它控制碳通过苯丙烷代谢途径进入特定的木质素，类黄酮和与壁结合的酚类生物合成途径的流量。尽管4CL在其他维管植物中已得到广泛表征，但对其在卷柏中的功能了解甚少。在这里，我们从卷柏卷柏中分离了两个4CL基因（Sm4CL1和Sm4CL2）。基于重组蛋白的酶活性，这两个基因均编码了真正的4CL。S. moellendorffii中的4CL亚型具有不同的活性：Sm4CL2比Sm4CL1更活跃。酶学性质和基因表达模式表明，4CL基因在维管植物的进化中是保守的。
• Rational Control of Polyketide Extender Units by Structure‐Based Engineering of a Crotonyl‐CoA Carboxylase/Reductase in Antimycin Biosynthesis
  作者：Lihan Zhang、Takahiro Mori、Qingfei Zheng、Takayoshi Awakawa、Yan Yan、Wen Liu、Ikuro Abe

  DOI：10.1002/anie.201506899

  日期：2015.11.2

  Bioengineering of natural product biosynthesis is a powerful approach to expand the structural diversity of bioactive molecules. However, in polyketide biosynthesis, the modification of polyketide extender units, which form the carbon skeletons, has remained challenging. Herein, we report the rational control of polyketide extender units by the structure‐based engineering of a crotonyl‐CoA carboxylase/reductase

  天然产物生物合成的生物工程是扩大生物活性分子结构多样性的有力方法。然而，在聚酮化合物的生物合成中，形成碳骨架的聚酮化合物增量剂单元的修饰仍然具有挑战性。本文中，我们报告了在抗霉素的生物合成中，通过巴豆酰-CoA羧化酶/还原酶（CCR）的基于结构的工程对聚酮化合物扩展单元的合理控制。CCR酶AntE的定点诱变，受以1.5Å分辨率解析的晶体结构的引导，通过V350G突变扩大了其底物范围，从而提供了吲哚基甲基丙二酰辅酶A。突变体A182L在常规还原过程中选择性催化了羧化反应。此外，带有AntE V350G的链霉菌菌株。这些发现加深了我们对CCRs分子机制的理解，CCRs将作为通用的生物催化剂来操纵结构单元，并为合理设计聚酮化合物的生物合成奠定了基础。
• Characterization and Functional Analysis of 4-Coumarate:CoA Ligase Genes in Mulberry
  作者：Chuan-Hong Wang、Jian Yu、Yu-Xiang Cai、Pan-Pan Zhu、Chang-Ying Liu、Ai-Chun Zhao、Rui-Hua Lü、Meng-Jiao Li、Feng-Xiang Xu、Mao-De Yu

  DOI：10.1371/journal.pone.0155814

  日期：——

  A small, multigene family encodes 4-coumarate:CoA ligases (4CLs) that catalyze the ligation of CoA to hydroxycinnamic acids, a branch point directing metabolites to flavonoid or monolignol pathways. In this study, we characterized four 4CL genes from M. notabilis Genome Database, and cloned four Ma4CL genes from M. atropurpurea cv. Jialing No.40. A tissue-specific expression analysis indicated that Ma4CL3 was expressed at higher levels than the other genes, and that Ma4CL3 was strongly expressed in root bark, stem bark, and old leaves. Additionally, the expression pattern of Ma4CL3 was similar to the trend of the total flavonoid content throughout fruit development. A phylogenetic analysis suggested that Mn4CL1, Mn4CL2, and Mn4CL4 belong to class I 4CLs, and Mn4CL3 belongs to class II 4CLs. Ma4CL genes responded differently to a series of stresses. Ma4CL3 expression was higher than that of the other Ma4CL genes following wounding, salicylic acid, and ultraviolet treatments. An in vitro enzyme assay indicated that 4-coumarate acid was the best substrate among cinnamic acid, 4-coumarate acid, and caffeate acid, but no catalytic activity to sinapate acid and ferulate acid. The results of subcellular localization experiments showed that Ma4CL3 localized to the cytomembrane, where it activated transcription. We used different vectors and strategies to fuse Ma4CL3 with stilbene synthase (STS) to construct four Ma4CL-MaSTS co-expression systems to generate resveratrol. The results indicated that only a transcriptional fusion vector, pET-Ma4CL3-T-MaSTS, which utilized a T7 promoter and lac operator for the expression of MaSTS, could synthesize resveratrol.

  一个由多个基因组成的小家族编码4-香豆酸：辅酶A连接酶（4CL），该酶催化辅酶A与羟基肉桂酸的连接，这是将代谢物导向黄酮或单木酚途径的分叉点。在这项研究中，我们描述了来自M. notabilis基因组数据库的四个4CL基因，并克隆了来自M. atropurpurea cv. Jialing No.40的四个Ma4CL基因。组织特异性表达分析表明，Ma4CL3的表达水平高于其他基因，并且在根皮、茎皮和旧叶中表达强烈。此外，Ma4CL3的表达模式与整个果实发育过程中总黄酮含量的趋势相似。系统发育分析表明，Mn4CL1、Mn4CL2和Mn4CL4属于I类4CL，而Mn4CL3属于II类4CL。Ma4CL基因对一系列胁迫的反应不同。在伤口、水杨酸和紫外线处理后，Ma4CL3的表达水平高于其他Ma4CL基因。体外酶分析表明，在肉桂酸、4-香豆酸和咖啡酸中，4-香豆酸是最好的底物，但对芥酸和阿魏酸没有催化活性。亚细胞定位实验结果表明，Ma4CL3定位于细胞膜，并在那里激活转录。我们使用不同的载体和策略将Ma