Radical intermediates in monooxygenase reactions of Rieske dioxygenases
Radical intermediates in monooxygenase reactions of Rieske dioxygenases
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DOI：
10.1021/ja068188v
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发表时间：
2007-03-28
影响因子：
15
通讯作者：
Lipscomb, John D.
中科院分区：
文献类型：
--
作者：
Chakrabarty, Sarmistha;Austin, Rachel N.;Lipscomb, John D.
Rieske双加氧酶催化多种芳香族化合物的顺式二羟基化反应，从而引发其生物降解。典型的Rieske双加氧酶萘1，2-双加氧酶（NDOS）催化萘双氧化形成（+）-顺式-（1 R，2S）-二羟基-1，2-二氢萘。NDOS由三种蛋白质组成：还原酶、铁氧还蛋白和α（3）β（3）加氧酶（NDO）。在每个α亚基中，NDO含有Rieske Fe 2S 2簇和单核铁位点，其中底物二羟基化发生。NDOS还催化许多底物的单加氧酶反应。该反应的机理对于单加氧酶或双加氧酶反应是未知的，但已经假定涉及结构特征的Fe（III）-氢过氧中间体或电子等效的Fe（V）-氧代-羟基中间体的直接反应，所述Fe（V）-氧代-羟基中间体在与底物反应之前通过O-O键裂解形成。前一种中间体的反应预计将通过阳离子中间体进行，而后者预计最初形成自由基中间体。在这里，单氧化反应的诊断探针分子，降冰片烷和双环己烷，进行了研究。在每种情况下，观察到显著量的衍生自自由基中间体的重排产物（寿命为11-18 ns），而很少或没有形成来自阳离子中间体的扩环产物。因此，这些分子的单氧化似乎通过Fe（V）-氧代-羟基中间体进行。这种高价中间体的形成表明，它也必须被认为是一个可能的参与者在双氧化反应，在计算研究相反，但在雅阁与以前的仿生研究。
Rieske dioxygenases catalyze the cis-dihydroxylation of a wide range of aromatic compounds to initiate their biodegradation. The archetypal Rieske dioxygenase naphthalene 1,2-dioxygenase (NDOS) catalyzes dioxygenation of naphthalene to form (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. NDOS is composed of three proteins: a reductase, a ferredoxin, and an alpha(3)beta(3) oxygenase (NDO). In each alpha subunit, NDO contains a Rieske Fe2S2 cluster and a mononuclear iron site where substrate dihydroxylation occurs. NDOS also catalyzes monooxygenase reactions for many substrates. The mechanism of the reaction is unknown for either the mono- or dioxygenase reactions but has been postulated to involve direct reaction of either a structurally characterized Fe(III)-hydroperoxy intermediate or the electronically equivalent Fe(V)-oxo-hydroxo intermediate formed by O-O bond cleavage before reaction with substrate. The reaction for the former intermediate is expected to proceed through cationic intermediates, while the latter is anticipated to initially form a radical intermediate. Here the monooxygenation reactions of the diagnostic probe molecules, norcarane and bicyclohexane, are investigated. In each case, a significant amount of the rearrangement product derived from a radical intermediate (lifetime of 11-18 ns) is observed, while little or no ring expansion product from a cationic intermediate is formed. Thus, monooxygenation of these molecules appears to proceed via the Fe(V)-oxo-hydroxo intermediate. The formation of this high-valent intermediate shows that it must also be considered as a possible participant in the dioxygenation reaction, in contrast to computational studies but in accord with previous biomimetic studies.