过氧中间体驱动二氧化酶中的碳键激活
Dirk Auman1, Felix Ecker2, Sophie L Mader1
1Department of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, Sweden.
Journal of the American Chemical Society
|August 18, 2022
概括
这项研究揭示了AsqJ酶中的一种新型过氧中间体,对于合成类有关键. 这一发现澄清了二氧化酶的机制,并表明阿尔法质酸盐可能并不总是被消耗.
科学领域:
- 生物化学
- 酵素学
- 有机化学
背景情况:
- 二氧化酶是生物和工业过程中氧气转移的重要酶.
- 对二氧化酶的精确化学机制,特别是对基质的修改,尚不完全了解.
- 一种依赖alpha- ketoglutarate的二氧化酶AsqJ可以合成重要的类.
研究的目的:
- 阐明昆醇生物合成中的AsqJ酶的分子机制.
- 确定参与AsqJ氧原子转移反应的关键中间体和催化物种.
- 了解由二氧化酶激活化学键的原理.
主要方法:
- 高分辨率的X射线晶体学以确定酶结构.
- 酶工程探测催化作用.
- 量子古典 (QM/MM) 模拟用于机械洞察.
- 生物化学测试以验证酶活性.
主要成果:
- 在AsqJ中发现了一种新型过氧介质,该介质将环素基质与活性位点金属离子连接起来.
- 基质环氧化通过这种中间体的同解裂变,产生高价值的费里尔 (FeIV=O) 物种.
- 催化循环可以在不消耗α-甲酸辅基质的情况下进行.
结论:
- 这项研究提供了AsqJ介导的类合成的详细分子机制.
- 这些发现为化学键激活和二氧化酶的功能提供了关键的见解.
- 这项工作促进了对酶反应网络及其药物相关性的理解.
相关概念视频
Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
6.1K
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
6.1K
Oxidative Cleavage of Alkenes: Ozonolysis
10.9K
In ozonolysis, ozone is used to cleave a carbon–carbon double bond to form aldehydes and ketones, or carboxylic acids, depending on the work-up.
Ozone is a symmetrical bent molecule stabilized by a resonance structure.
Ozone is a symmetrical bent molecule stabilized by a resonance structure.
10.9K
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
10.7K
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
10.7K
Oxidation of Phenols to Quinones
3.4K
In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...
3.4K
Pyruvate Oxidation
160.8K
After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
160.8K
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
6.2K
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
6.2K


