6-[(3-Acetyl-4,5,7-trihydroxynaphthalen-2-yl)methyl]-4-hydroxypyran-2-one | 1126273-95-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-[(3-Acetyl-4,5,7-trihydroxynaphthalen-2-yl)methyl]-4-hydroxypyran-2-one
• 英文别名: 6-[(3-acetyl-4,5,7-trihydroxynaphthalen-2-yl)methyl]-4-hydroxypyran-2-one
• CAS: 1126273-95-7
• 化学式: C₁₈H₁₄O₇
• 分子量: 342.305
• InChiKey: JTBDOMBWPMZTLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  sodium malonate 在 PKS₄ minimal polyketide synthase 、 Rhizobium trifolii malonyl-CoA synthase MatB 、 5’-三磷酸腺苷 、 辅酶 A 、 magnesium chloride 、 1,4-二巯基-2,3-丁二醇 作用下， 反应 12.0h， 生成 2-acetonyl-8,10-dihydroxy-5-methyl-4H-naphtho[1,2-b]pyran-4-one 、 6-[(3-Acetyl-4,5,7-trihydroxynaphthalen-2-yl)methyl]-4-hydroxypyran-2-one
  参考文献：
  名称：

  Classification, Prediction, and Verification of the Regioselectivity of Fungal Polyketide Synthase Product Template Domains

  摘要：

  The fungal iterative nonreducing polyketide synthases (NRPKSs) synthesize aromatic polyketides, many of which have important biological activities. The product template domains (PT) embedded in the multidomain NRPKSs mediate the regio-selective cyclization of the highly reactive polyketide backbones and dictate the final structures of the products. Understanding the sequence-activity relationships of different PT domains is therefore an important step toward the prediction of polyketide structures from NRPKS sequences and can enable the genome mining of hundreds of cryptic NRPKSs uncovered via genome sequencing. In this work, we first performed phylogenetic analysis of PT domains from NRPKSs of known functions and showed that the PT domains can be classified into five groups, with each group corresponding to a unique product size or cyclization regioselectivity. Group V contains the formerly unverified PT domains that were identified as C6-C11 aldol cyclases. The regioselectivity of PTs from this group were verified by product-based assays using the PT domain excised from the asperthecin AptA NRPKS. When combined with dissociated PKS4 minimal PKS, or replaced the endogenous PKS4 C2-C7 PT domain in a hybrid NRPKS, AptA-PT directed the C6-C11 cyclization of the nonaketide backbone to yield a tetracyclic pyranoanthraquinone 4. Extensive NMR analysis verified that the backbone of 4 was indeed cyclized with the expected regioselectivity. The PT phylogenetic analysis was then expanded to include similar to 100 PT sequences from unverified NRPKSs. Using the assays developed for AptA-PT, the regioselectivities of additional PT domains were investigated and matched to those predicted by the phylogenetic classifications.

  DOI：

  10.1074/jbc.m110.128504

文献信息

• Structural and Biochemical Characterization of ZhuI Aromatase/Cyclase from the R1128 Polyketide Pathway
  作者：Brian D. Ames、Ming-Yue Lee、Colleen Moody、Wenjun Zhang、Yi Tang、Shiou-Chuan Tsai

  DOI：10.1021/bi200593m

  日期：2011.10.4

  Aromatic polyketides comprise an important class of natural products that possess a wide range of biological activities. The cyclization of the polyketide chain is a critical control point in the biosynthesis of aromatic polyketides. The aromatase/cyclases (ARO/CYCs) are an important component of the type II polyketide synthase (PKS) and help fold the polyketide for regiospecific cyclizations of the

  芳香族聚酮化合物是一类重要的天然产物，具有广泛的生物活性。聚酮链的环化是芳香族聚酮生物合成的关键控制点。芳香酶/环化酶 (ARO/CYC) 是 II 型聚酮化合物合酶 (PKS) 的重要组成部分，有助于折叠聚酮化合物以进行第一环和/或芳香化的区域特异性环化，促进两种常见的第一环环化模式细菌 II 型 PKS：C7-C12 和 C9-C14。我们之前已经报道了 TcmN ARO/CYC 的晶体结构和酶学分析，它促进了 C9-C14 的首环环化。然而，如何控制 C7-C12 首环环化仍未解决。在这项工作中，我们展示了 ZhuI 的 2.4 Å 晶体结构，来自负责产生 R1128 聚酮化合物的 II 型 PKS 途径的 C7-C12 特异性第一环 ARO/CYC。尽管 ZhuI 具有 TcmN ARO/CYC 共享的螺旋握把折叠，但在整体结构和口袋残基组成方面存在显着差异，这对于指导 C7-C12（而不是
• Insight into the Molecular Basis of Aromatic Polyketide Cyclization: Crystal Structure and in Vitro Characterization of WhiE-ORFVI
  作者：Ming-Yue Lee、Brian D. Ames、Shiou-Chuan Tsai

  DOI：10.1021/bi201705q

  日期：2012.4.10

  Aromatic polyketides are biologically active natural products. Many important pharmaceuticals are derived from aromatic polyketides. Especially important in aromatic polyketide biosynthesis is the regiospecific cyclization of a linear, preassembled polyketide chain catalyzed by aromatase/cyclase (ARO/CYC), which serves as a key control point in aromatic ring formation. How different ARO/CYCs promote different cyclization patterns is not well understood. The whiE locus of Streptomyces coelicolor A3(2) is responsible for the biosynthesis of an aromatic polyketide precursor to the gray spore pigment. The WhiE ARO/CYC catalyzes the regiospecific C9-C14 and C7-C16 cyclization and aromatization of a 24-carbon polyketide chain. WhiE ARO/CYC shares a high degree of similarity to another nonreducing PKS ARO/CYC, TcmN ARO/CYC. This paper presents the apo crystal structure of WhiE ARO/CYC, and cocrystal structures of WhiE and TcmN ARO/CYCs bound with polycyclic aromatic compounds that mimic the respective ARO/CYC products. Site-directed mutagenesis coupled with in vitro PKS reconstitution assays was used to characterize the interior pocket residues of WhiE ARO/CYC. The results confirmed that the Interior pocket of ARO/CYCs is a critical determinant of polyketide cyclization specificity. A unified ARO/CYC-mediated cyclization mechanism is proposed on the basis of these structural and functional results.