6'-羟基七苯酚 | 2168-61-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 6'-羟基七苯酚
• 英文名称: 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione
• 英文别名: 3,4-dihydroxy-9,10-secoandrost-1,3,5(10)-triene-9,17-dione；3,4-DHSA；(3aS,4S,7aS)-4-[2-(2,3-dihydroxy-6-methylphenyl)ethyl]-7a-methyl-2,3,3a,4,6,7-hexahydroindene-1,5-dione
• CAS: 2168-61-8
• 化学式: C₁₉H₂₄O₄
• 分子量: 316.397
• InChiKey: YUHVBHDSVLKFNI-NJSLBKSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6'-羟基七苯酚 、 氧气 生成 (1E,2Z)-3-hydroxy-5,9,17-trioxo-4,5:9,10-disecoandrosta-1(10),2-dien-4-oate 、 氢(+1)阳离子
  参考文献：
  名称：

  Gene Encoding the Hydrolase for the Product of the meta -Cleavage Reaction in Testosterone Degradation by Comamonas testosteroni

  摘要：

  摘要 在之前的一项研究中，我们分离出了 元 裂解酶基因、 tesB 该基因编码一种执行 元 -睾酮分解过程中进行元清除反应的酶。 睾酮分解过程中进行元清除反应的酶。 TA441（M. Horinouchi 等人，《微生物学》147：3367-3375，2001 年）。在此，我们报告了一种基因的分离结果、 tesD 该基因编码一种水解酶，可作用于 元 -水解反应的产物。我们分离出了 tesD 通过使用 Tn 5 突变体 TA441 分离出了 tesD，该突变体在睾酮的作用下生长受限。TesD 与假单胞菌中已知的联苯降解水解酶 BphDs 的氨基酸序列有大约 40% 的相同性。 假单胞菌 TesD 断裂突变体在睾酮上的生长有限，培养物呈浓黄色。高压液相色谱法分析了与睾酮一起培养的 TesD 中断突变体的培养物，检测到五种主要的中间化合物，其中一种在中性条件下呈黄色，被认为是睾酮降解过程中的产物。 元 -甲基化反应的产物。经分析鉴定，甲基化产物为甲基-4,5-9,10-二癸基-3-甲氧基-5,9,17-三氧雄甾烷-1(10),2-二烯-4-酸，表明 TesD 降解睾酮的底物是 4,5-9,10-二癸基-3-羟基-5,9,17-三氧雄甾烷-1(10),2-二烯-4-酸。4,5-9,10-二癸酸-3-羟基-5,9,17-三氧雄甾烷-1(10),2-二烯-4-酸由大肠杆菌转化而来。 大肠杆菌 表达 TesD。在 下游 的下游，我们发现了 tesE , F 和 G 编码的酶能降解由 TesD 转化的 4,5-9,10-二癸-3-羟基-5,9,17-三氧代雄甾烷-1(10),2-二烯-4-酸的产物之一。

  DOI：

  10.1128/aem.69.4.2139-2152.2003
• 作为产物：
  描述：

  开环苯酚 在 recombinant Mycobacterium tuberculosis 3-hydroxy-9,10-seconandrost-1,3,5⁽¹⁰⁾-triene-9,17-dione 4-hydroxylase 、 氧气 、 2,6-蒽二酚 、 还原型辅酶Ⅰ 作用下， 以 水 为溶剂， 生成 6'-羟基七苯酚
  参考文献：
  名称：

  A Flavin-dependent Monooxygenase from Mycobacterium tuberculosis Involved in Cholesterol Catabolism

  摘要：

  Mycobacterium tuberculosis (Mtb) and Rhodococcus jostii RHA1 have similar cholesterol catabolic pathways. This pathway contributes to the pathogenicity of Mtb. The hsaAB cholesterol catabolic genes have been predicted to encode the oxygenase and reductase, respectively, of a flavin-dependent mono-oxygenase that hydroxylates 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17- dione (3-HSA) to a catechol. An hsaA deletion mutant of RHA1 did not grow on cholesterol but transformed the latter to 3-HSA and related metabolites in which each of the two keto groups was reduced: 3,9-dihydroxy-9,10-seconandrost-1,3,5(10)-triene- 17-one (3,9-DHSA) and 3,17-dihydroxy-9,10-seconandrost-1,3,5( 10)-triene-9-one (3,17-DHSA). Purified 3-hydroxy-9,10- seconandrost-1,3,5(10)-triene-9,17-dione 4-hydroxylase (HsaAB) from Mtb had higher specificity for 3-HSA than for 3,17-DHSA (apparent k(cat)/K-m =1000 +/- 100 M-1 s(-1) versus 700 +/- 100 M-1 s(-1)). However, 3,9-DHSA was a poorer substrate than 3-hydroxybiphenyl (apparent k(cat)/K-m = 80 +/- 40 M-1 s(-1)). In the presence of 3-HSA the K-mapp for O-2 was 100 +/- 10 mu M. The crystal structure of HsaA to 2.5-angstrom resolution revealed that the enzyme has the same fold, flavin-binding site, and catalytic residues as p-hydroxyphenyl acetate hydroxylase. However, HsaA has a much larger phenol-binding site, consistent with the enzyme's substrate specificity. In addition, a second crystal form of HsaA revealed that a C-terminal flap (Val(367)-Val(394)) could adopt two conformations differing by a rigid body rotation of 25 degrees around Arg(366). This rotation appears to gate the likely flavin entrance to the active site. In docking studies with 3-HSA and flavin, the closed conformation provided a rationale for the enzyme's substrate specificity. Overall, the structural and functional data establish the physiological role of HsaAB and provide a basis to further investigate an important class of monooxygenases as well as the bacterial catabolism of steroids.

  DOI：

  10.1074/jbc.m109.099028

文献信息

• METHODS AND AGENTS FOR TREATING TUBERCULOSIS
  申请人：Eltis Lindsay D.

  公开号：US20100041631A1

  公开（公告）日：2010-02-18

  The present invention relates to the treatment of tuberculosis (mycobacterial infections) by the use of KshAB complex inhibitors, or a KstD molecule, or a HsaAB complex, or a HsaC molecule, or a HsaD molecule. The application also includes a method for identifying an inhibitor or modulator of the previously mentioned molecules and complexes.

  本发明涉及使用KshAB复合物抑制剂、KstD分子、HsaAB复合物、HsaC分子或HsaD分子治疗结核病（分枝杆菌感染）。该申请还包括一种鉴定前述分子和复合物的抑制剂或调节剂的方法。
• Studies of a Ring-Cleaving Dioxygenase Illuminate the Role of Cholesterol Metabolism in the Pathogenesis of Mycobacterium tuberculosis
  作者：Katherine C. Yam、Igor D'Angelo、Rainer Kalscheuer、Haizhong Zhu、Jian-Xin Wang、Victor Snieckus、Lan H. Ly、Paul J. Converse、William R. Jacobs、Natalie Strynadka、Lindsay D. Eltis

  DOI：10.1371/journal.ppat.1000344

  日期：——

  Mycobacterium tuberculosis, the etiological agent of TB, possesses a cholesterol catabolic pathway implicated in pathogenesis. This pathway includes an iron-dependent extradiol dioxygenase, HsaC, that cleaves catechols. Immuno-compromised mice infected with a ΔhsaC mutant of M. tuberculosis H37Rv survived 50% longer than mice infected with the wild-type strain. In guinea pigs, the mutant disseminated more slowly to the spleen, persisted less successfully in the lung, and caused little pathology. These data establish that, while cholesterol metabolism by M. tuberculosis appears to be most important during the chronic stage of infection, it begins much earlier and may contribute to the pathogen's dissemination within the host. Purified HsaC efficiently cleaved the catecholic cholesterol metabolite, DHSA (3,4-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione; kcat/Km = 14.4±0.5 µM−1 s−1), and was inactivated by a halogenated substrate analogue (partition coefficient<50). Remarkably, cholesterol caused loss of viability in the ΔhsaC mutant, consistent with catechol toxicity. Structures of HsaC:DHSA binary complexes at 2.1 Å revealed two catechol-binding modes: bidentate binding to the active site iron, as has been reported in similar enzymes, and, unexpectedly, monodentate binding. The position of the bicyclo-alkanone moiety of DHSA was very similar in the two binding modes, suggesting that this interaction is a determinant in the initial substrate-binding event. These data provide insights into the binding of catechols by extradiol dioxygenases and facilitate inhibitor design.

  结核分枝杆菌是结核病的病原体，它具有与发病机理相关的胆固醇分解代谢途径。该途径包括一种铁依赖性外二醇双加氧酶（HsaC），可分解儿茶酚。免疫功能受损的小鼠感染了结核分枝杆菌H37Rv的ΔhsaC突变体后，存活时间比感染野生型菌株的小鼠长50%。在豚鼠身上，突变体向脾脏扩散的速度较慢，在肺部的存活能力较差，且几乎不会引起病理反应。这些数据表明，虽然结核分枝杆菌的胆固醇代谢在感染的慢性阶段似乎最为重要，但它实际上在更早的阶段就开始了，并可能有助于病原体在宿主体内的扩散。纯化的HsaC可有效分解儿茶酚胆固醇代谢产物DHSA（3,4-二羟基-9,10-二氢雄甾-1,3,5(10)-三烯-9,17-二酮；kcat/Km=14.4±0.5 µM-1 s-1），并被卤代底物类似物（分配系数<50）灭活。值得注意的是，胆固醇会导致ΔhsaC突变体失去活性，这与儿茶酚的毒性一致。HsaC：DHSA二元复合物的结构在2.1 Å处显示有两种儿茶酚结合模式：与类似
• A gene cluster encoding cholesterol catabolism in a soil actinomycete provides insight into <i>Mycobacterium tuberculosis</i> survival in macrophages
  作者：Robert Van der Geize、Katherine Yam、Thomas Heuser、Maarten H. Wilbrink、Hirofumi Hara、Matthew C. Anderton、Edith Sim、Lubbert Dijkhuizen、Julian E. Davies、William W. Mohn、Lindsay D. Eltis

  DOI：10.1073/pnas.0605728104

  日期：2007.2.6

  Rhodococcus sp. strain RHA1, a soil bacterium related to Mycobacterium tuberculosis , degrades an exceptionally broad range of organic compounds. Transcriptomic analysis of cholesterol-grown RHA1 revealed a catabolic pathway predicted to proceed via 4-androstene-3,17-dione and 3,4-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione (3,4-DHSA). Inactivation of each of the hsaC , supAB , and mce4 genes in RHA1 substantiated their roles in cholesterol catabolism. Moreover, the hsaC ⁻ mutant accumulated 3,4-DHSA, indicating that HsaC _RHA1 , formerly annotated as a biphenyl-degrading dioxygenase, catalyzes the oxygenolytic cleavage of steroid ring A. Bioinformatic analyses revealed that 51 rhodococcal genes specifically expressed during growth on cholesterol, including all predicted to specify the catabolism of rings A and B, are conserved within an 82-gene cluster in M. tuberculosis H37Rv and Mycobacterium bovis bacillus Calmette–Guérin. M. bovis bacillus Calmette–Guérin grew on cholesterol, and hsaC and kshA were up-regulated under these conditions. Heterologously produced HsaC _H37Rv and HsaD _H37Rv transformed 3,4-DHSA and its ring-cleaved product, respectively, with apparent specificities ≈40-fold higher than for the corresponding biphenyl metabolites. Overall, we annotated 28 RHA1 genes and proposed physiological roles for a similar number of mycobacterial genes. During survival of M. tuberculosis in the macrophage, these genes are specifically expressed, and many appear to be essential. We have delineated a complete suite of genes necessary for microbial steroid degradation, and pathogenic mycobacteria have been shown to catabolize cholesterol. The results suggest that cholesterol metabolism is central to M. tuberculosis 's unusual ability to survive in macrophages and provide insights into potential targets for novel therapeutics.

  Rhodococcus sp.菌株RHA1是一种与结核分枝杆菌相关的土壤细菌，能够降解异常广泛的有机化合物。对以胆固醇为生长基质的RHA1进行转录组分析，预测其通过4-雄烯-3,17-二酮和3,4-二羟基-9,10-二氢-9,17-二酮（3,4-DHSA）进行降解。在RHA1中失活每个hsaC、supAB和mce4基因，证实它们在胆固醇分解中的作用。此外，hsaC-突变体积累了3,4-DHSA，表明HsaC RHA1，曾被注释为二苯基降解双氧水化酶，催化类固醇环A的氧解裂。生物信息学分析表明，在生长于胆固醇上时，51个rhodococcal基因，包括所有预测的环A和环B降解的基因，都在M. tuberculosis H37Rv和Mycobacterium bovis卡尔梅特-古林杆菌的82个基因簇中保守。M. bovis卡尔梅特-古林杆菌在胆固醇上生长，而在这些条件下，hsaC和kshA上调。异源表达的HsaC H37Rv和HsaD H37Rv转化了3,4-DHSA及其环裂解产物，其表观特异性约为相应的二苯基代谢物的40倍。总体而言，我们注释了28个RHA1基因，并提出了同样数量的结核分枝杆菌基因的生理作用。在结核分枝杆菌在巨噬细胞中生存时，这些基因被特异性地表达，许多基因似乎是必不可少的。我们已经勾勒出微生物类固醇降解所必需的完整基因组，并证明了致病分枝杆菌能够降解胆固醇。结果表明，胆固醇代谢对结核分枝杆菌在巨噬细胞中存活的不寻常能力至关重要，并提供了潜在的新型治疗靶点的见解。
• Silk-Based Adhesives
  申请人：Trustees of Tufts College

  公开号：US20180361015A1

  公开（公告）日：2018-12-20

  In some embodiments, the present invention provides compositions including silk fibroin, at least one hydrophilic agent, and at least one catechol donating agent, wherein the at least one hydrophilic agent and at least one catechol donating agent are conjugated to the silk fibroin. According to various embodiments, at least a portion of the silk fibroin may be crosslinked. In some embodiments, the silk fibroin is at least 50% (e.g., 60%, 70%, 80%, 90%, 95% or more) crosslinked. In some embodiments, the present invention also provides methods for making such compositions.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.