1,4-dihydroxynaphthoyl-CoA | 875613-67-5

• 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: 1,4-dihydroxynaphthoyl-CoA
• 英文别名: 1,4-dihydroxy-2-naphtoyl coenzyme A；1,4-dihydroxy-2-naphtoyl-CoA；1,4-Dihydroxy-2-naphthoyl-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] 1,4-dihydroxynaphthalene-2-carbothioate
• CAS: 875613-67-5
• 化学式: C₃₂H₄₂N₇O₁₉P₃S
• 分子量: 953.708
• InChiKey: PYTINLGPKDJURZ-HSJNEKGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  62
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  429
• 氢给体数：
  11
• 氢受体数：
  24

反应信息

• 作为产物：
  描述：

  在 Escherichia coli 1,4-dihydroxy-2-naphtoyl coenzyme A synthase, wild-type 、 Escherichia coli MenC enzyme 、 Escherichia coli MenE enzyme 、 5’-三磷酸腺苷 、 辅酶 A 、 magnesium chloride 作用下， 生成 1,4-dihydroxynaphthoyl-CoA
  参考文献：
  名称：

  A Bicarbonate Cofactor Modulates 1,4-Dihydroxy-2-naphthoyl-Coenzyme A Synthase in Menaquinone Biosynthesis of Escherichia coli

  摘要：

  1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase is a typical crotonase-fold protein catalyzing an intramolecular Claisen condensation in the menaquinone biosynthetic pathway. We have characterized this enzyme from Escherichia coli and found that it is activated by bicarbonate in a concentration-dependent manner. The bicarbonate binding site has been identified in the crystal structure of a virtually identical ortholog (96.8% sequence identity) from Salmonella typhimurium through comparison with a bicarbonate-insensitive orthologue. Kinetic properties of the enzyme and its site-directed mutants of the bicarbonate binding site indicate that the exogenous bicarbonate anion is essential to the enzyme activity. With this essential catalytic role, the simple bicarbonate anion is an enzyme cofactor, which is usually a small organic molecule derived from vitamins, a metal ion, or a metal-containing polyatomic anionic complex. This finding leads to classification of the DHNA-CoA synthases into two evolutionarily conserved subfamilies: type I enzymes that are bicarbonate-dependent and contain a conserved glycine at the bicarbonate binding site; and type II enzymes that are bicarbonate-independent and contain a conserved aspartate at the position similar to the enzyme-bound bicarbonate. In addition, the unique location of the enzyme-bound bicarbonate allows it to be proposed as a catalytic base responsible for abstraction of the alpha-proton of the thioester substrate in the enzymatic reaction, suggesting a unified catalytic mechanism for all DHNA-CoA synthases.

  DOI：

  10.1074/jbc.m110.147702

文献信息

• [EN] INHIBITORS OF ADENYLATE-FORMING ENZYME MENE<br/>[FR] INHIBITEURS DE L'ENZYME MENE FORMANT L'ADÉNYLATE CYCLASE
  申请人：MEMORIAL SLOAN KETTERING CANCER CENTER

  公开号：WO2020163673A1

  公开（公告）日：2020-08-13

  Provided herein are compounds of Formula (I) and pharmaceutically acceptable salts or tautomers thereof which may inhibit adenylate-forming enzymes. Also provided are pharmaceutical compositions, kits, uses, and methods involving the inventive compounds for the treatment and/or prevention of an infectious disease (e.g., bacterial infection (e.g., tuberculosis, methicillin- resistant Staphylococcus aureus)).

  本文提供了式（I）的化合物及其药用可接受的盐或互变异构体，这些化合物可能抑制腺苷酸形成酶。还提供了涉及这些创新化合物用于治疗和/或预防传染病（例如细菌感染（例如结核病、耐甲氧西林金黄色葡萄球菌））的药物组合物、试剂盒、用途和方法。
• MICROORGANISMS AND METHODS FOR THE PRODUCTION OF CAPROLACTONE
  申请人：Burgard Anthony P.

  公开号：US20130144029A1

  公开（公告）日：2013-06-06

  The invention provides non-naturally occurring microbial organisms containing caprolactone pathways having at least one exogenous nucleic acid encoding a butadiene pathway enzyme expressed in a sufficient amount to produce caprolactone. The invention additionally provides methods of using such microbial organisms to produce caprolactone by culturing a non-naturally occurring microbial organism containing caprolactone pathways as described herein under conditions and for a sufficient period of time to produce caprolactone.

  本发明提供了含有环己内酯代谢途径的非自然微生物体，其中至少含有一种外源核酸编码丁二烯代谢途径酶的表达量足以产生环己内酯。此外，本发明还提供了使用这种微生物体生产环己内酯的方法，即在适当的条件下并足够长的时间内培养含有环己内酯代谢途径的非自然微生物体，以产生环己内酯。
• Microorganisms for Producing Cyclohexanone and Methods Related Thereto
  申请人：Burgard Anthony

  公开号：US20120329111A1

  公开（公告）日：2012-12-27

  Provided herein is a non-naturally occurring microbial organism having a cyclohexanone pathway and comprising at least one exogenous nucleic acid encoding a cyclohexanone pathway enzyme. Also provided herein is a method for producing cyclohexanone, including culturing these non-naturally occurring microbial organisms.

  本文提供了一种非自然存在的微生物生物体，具有环己酮途径，并且包含至少一个外源核酸编码环己酮途径酶。还提供了一种生产环己酮的方法，包括培养这些非自然存在的微生物生物体。
• ORGANISMS FOR THE PRODUCTION OF CYCLOHEXANONE
  申请人：Genomatica, Inc.

  公开号：US20140356919A1

  公开（公告）日：2014-12-04

  A non-naturally occurring microbial organism has cyclohexanone pathways that include at least one exogenous nucleic acid encoding a cyclohexanone pathway enzyme. A pathway includes a 2-ketocyclohexane-1-carboxyl-CoA hydrolase (acting on C—C bond), a 2-ketocyclohexane-1-carboxylate decarboxylase and an enzyme selected from a 2-ketocyclohexane-1-carboxyl-CoA hydrolase (acting on thioester), a 2-ketocyclohexane-1-carboxyl-CoA transferase, and a 2-ketocyclohexane-1-carboxyl-CoA synthetase. A pathway includes an enzyme selected from a 6-ketocyclohex-1-ene-1-carboxyl-CoA hydrolase (acting on C—C bond), a 6-ketocyclohex-1-ene-1-carboxyl-CoA synthetase, a 6-ketocyclohex-1-ene-1-carboxyl-CoA hydrolase (acting on thioester), a 6-ketocyclohex-1-ene-1-carboxyl-CoA transferase, a 6-ketocyclohex-1-ene-1-carboxyl-CoA reductase, a 6-ketocyclohex-1-ene-1-carboxylate decarboxylase, a 6-ketocyclohex-1-ene-1-carboxylate reductase, a 2-ketocyclohexane-1-carboxyl-CoA synthetase, a 2-ketocyclohexane-1-carboxyl-CoA transferase, a 2-ketocyclohexane-1-carboxyl-CoA hydrolase (acting on thioester), a 2-ketocyclohexane-1-carboxylate decarboxylase, and a cyclohexanone dehydrogenase. A pathway includes an adipate semialdehyde dehydratase, a cyclohexane-1,2-diol dehydrogenase, and a cyclohexane-1,2-diol dehydratase. A pathway includes a 3-oxopimelate decarboxylase, a 4-acetylbutyrate dehydratase, a 3-hydroxycyclohexanone dehydrogenase, a 2-cyclohexenone hydratase, a cyclohexanone dehydrogenase and an enzyme selected from a 3-oxopimeloyl-CoA synthetase, a 3-oxopimeloyl-CoA hydrolase (acting on thioester), and a 3-oxopimeloyl-coA transferase. Each these pathways can include a PEP carboxykinase. A method for producing cyclohexanone includes culturing these non-naturally occurring microbial organisms.

  一种非自然存在的微生物有环己酮途径，其中至少包括一个外源性核酸编码一个环己酮途径酶。途径包括一个2-酮环己烷-1-羧酸-辅酶A水解酶（作用于C-C键），一个2-酮环己烷-1-羧酸脱羧酶和从2-酮环己烷-1-羧酸-辅酶A水解酶（作用于硫酯），2-酮环己烷-1-羧酸-辅酶A转移酶和2-酮环己烷-1-羧酸-辅酶A合成酶中选择的酶。途径包括从6-酮环己-1-烯-1-羧酸-辅酶A水解酶（作用于C-C键），6-酮环己-1-烯-1-羧酸-辅酶A合成酶，6-酮环己-1-烯-1-羧酸-辅酶A水解酶（作用于硫酯），6-酮环己-1-烯-1-羧酸-辅酶A转移酶，6-酮环己-1-烯-1-羧酸-辅酶A还原酶，6-酮环己-1-烯-1-羧酸脱羧酶，6-酮环己-1-烯-1-羧酸还原酶，2-酮环己烷-1-羧酸-辅酶A合成酶，2-酮环己烷-1-羧酸-辅酶A转移酶，2-酮环己烷-1-羧酸-辅酶A水解酶（作用于硫酯），2-酮环己烷-1-羧酸脱羧酶和环己酮脱氢酶中选择的酶。途径包括己二酸半醛脱水酶、环己-1,2-二醇脱氢酶和环己-1,2-二醇脱水酶。途径包括3-氧戊二酸脱羧酶、4-醋酰丁酸脱水酶、3-羟基环己酮脱氢酶、2-环己烯酮水合酶、环己酮脱氢酶和从3-氧戊二酰辅酶A合成酶、3-氧戊二酰辅酶A水解酶（作用于硫酯）和3-氧戊二酰辅酶A转移酶中选择的酶。这些途径中每个都可以包括PEP羧激酶。一种制备环己酮的方法包括培养这些非自然存在的微生物。
• Microorganisms and methods for the production of caprolactone
  申请人：GENOMATICA, INC.

  公开号：US10351887B2

  公开（公告）日：2019-07-16

  The invention provides non-naturally occurring microbial organisms containing caprolactone pathways having at least one exogenous nucleic acid encoding a butadiene pathway enzyme expressed in a sufficient amount to produce caprolactone. The invention additionally provides methods of using such microbial organisms to produce caprolactone by culturing a non-naturally occurring microbial organism containing caprolactone pathways as described herein under conditions and for a sufficient period of time to produce caprolactone.

  本发明提供了含有己内酯途径的非天然存在的微生物有机体，该有机体具有至少一种编码丁二烯途径酶的外源核酸，其表达量足以生产己内酯。本发明还提供了使用这种微生物生物生产己内酯的方法，即在生产己内酯的条件下，培养含有本文所述己内酯途径的非天然存在的微生物生物足够长的时间，以生产己内酯。