Buckel Wolfgang, Zhang Jin, Friedrich Peter, Parthasarathy Anutthaman, Li Huan, Djurdjevic Ivana, Dobbek Holger, Martins Berta M
Max-Planck-Institut für terrestrische Mikrobiologie, 35043 Marburg, Germany.
Biochim Biophys Acta. 2012 Nov;1824(11):1278-90. doi: 10.1016/j.bbapap.2011.11.009. Epub 2011 Dec 8.
The steadily increasing field of radical biochemistry is dominated by the large family of S-adenosylmethionine dependent enzymes, the so-called radical SAM enzymes, of which several new members are discovered every year. Here we report on 2- and 4-hydroxyacyl-CoA dehydratases which apply a very different method of radical generation. In these enzymes ketyl radicals are formed by one-electron reduction or oxidation and are recycled after each turnover without further energy input. Earlier reviews on 2-hydroxyacyl-CoA dehydratases were published in 2004 [J. Kim, M. Hetzel, C.D. Boiangiu, W. Buckel, FEMS Microbiol. Rev. 28 (2004) 455-468. W. Buckel, M. Hetzel, J. Kim, Curr. Opin. Chem. Biol. 8 (2004) 462-467.]
The review focuses on four types of 2-hydroxyacyl-CoA dehydratases that are involved in the fermentation of amino acids by anaerobic bacteria, especially clostridia. These enzymes require activation by one-electron transfer from an iron-sulfur protein driven by hydrolysis of ATP. The review further describes the proposed mechanism that is highlighted by the identification of the allylic ketyl radical intermediate and the elucidation of the crystal structure of 2-hydroxyisocapryloyl-CoA dehydratase. With 4-hydroxybutyryl-CoA dehydratase the crystal structure, the complete stereochemistry and the function of several conserved residues around the active site could be identified. Finally potential biotechnological applications of the radical dehydratases are presented.
The action of the activator as an 'Archerase' shooting electrons into difficultly reducible acceptors becomes an emerging principle in anaerobic metabolism. The dehydratases may provide useful tools in biotechnology. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.
自由基生物化学领域不断发展，其中以依赖S-腺苷甲硫氨酸的酶大家族为主导，即所谓的自由基SAM酶，每年都会发现几个新成员。在此，我们报道2-和4-羟基酰基辅酶A脱水酶，它们采用一种截然不同的自由基生成方法。在这些酶中，酮基自由基通过单电子还原或氧化形成，并且在每次周转后无需进一步能量输入即可循环利用。关于2-羟基酰基辅酶A脱水酶的早期综述发表于2004年[J. Kim, M. Hetzel, C.D. Boiangiu, W. Buckel, FEMS Microbiol. Rev. 28 (2004) 455 - 468. W. Buckel, M. Hetzel, J. Kim, Curr. Opin. Chem. Biol. 8 (2004) 462 - 467.]
本综述聚焦于厌氧细菌，尤其是梭菌属，在氨基酸发酵过程中涉及的四种类型的2-羟基酰基辅酶A脱水酶。这些酶需要由ATP水解驱动的铁硫蛋白进行单电子转移来激活。该综述进一步描述了所提出的机制，这一机制因烯丙基酮基自由基中间体的鉴定以及2-羟基异辛酰辅酶A脱水酶晶体结构的阐明而得以突出。对于4-羟基丁酰辅酶A脱水酶，已确定了其晶体结构、完整的立体化学以及活性位点周围几个保守残基的功能。最后介绍了自由基脱水酶潜在的生物技术应用。
激活剂作为“箭酶”向难以还原的受体发射电子的作用，正成为厌氧代谢中的一个新兴原理。这些脱水酶可能在生物技术中提供有用的工具。本文是名为“自由基SAM酶与自由基酶学”的特刊的一部分。
