The Enigmatic P450 Decarboxylase OleT Is Capable of, but Evolved To Frustrate, Oxygen Rebound Chemistry.
The Enigmatic P450 Decarboxylase OleT Is Capable of, but Evolved To Frustrate, Oxygen Rebound Chemistry.
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DOI：
10.1021/acs.biochem.7b00338
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发表时间：
2017-07-05
期刊：
影响因子：
2.9
通讯作者：
Makris TM
中科院分区：
文献类型：
--
作者：
Hsieh CH;Huang X;Amaya JA;Rutland CD;Keys CL;Groves JT;Austin RN;Makris TM
OleT是一种细胞色素P450酶，其催化从可变链长脂肪酸中除去二氧化碳以形成1-烯烃。在这项工作中，我们研究了OleT与可形成液体运输燃料的较短链长（n ≤ 12）脂肪酸的结合和代谢概况。瞬态动力学和产物分析证实，OleT能够用较短的底物活化过氧化氢以形成高价中间体化合物I，并在很大程度上进行C-C键断裂。然而，该酶还使用通常与将氧插入烃中相关的高价铁含氧化学产生脂肪醇副产物。当存在可引发化合物I形成的短链脂肪酸时，OleT以使人想起许多β-羟化酶与自由基时钟底物的反应的方式氧化诊断探针分子降冰片烷和甲基环丙烷。这些数据与化合物I在初始步骤中提取底物氢原子的脱羧机制一致。定位的初始基板自由基是一个关键因素，在控制活性OH反弹的效率。
OleT is a cytochrome P450 enzyme that catalyzes the removal of carbon dioxide from variable chain length fatty acids to form 1-alkenes. In this work, we examine the binding and metabolic profile of OleT with shorter chain length (n ≤ 12) fatty acids that can form liquid transportation fuels. Transient kinetics and product analyses confirm that OleT capably activates hydrogen peroxide with shorter substrates to form the high-valent intermediate Compound I and largely performs C–C bond scission. However, the enzyme also produces fatty alcohol side products using the high-valent iron oxo chemistry commonly associated with insertion of oxygen into hydrocarbons. When presented with a short chain fatty acid that can initiate the formation of Compound I, OleT oxidizes the diagnostic probe molecules norcarane and methylcyclopropane in a manner that is reminiscent of reactions of many CYP hydroxylases with radical clock substrates. These data are consistent with a decarboxylation mechanism in which Compound I abstracts a substrate hydrogen atom in the initial step. Positioning of the incipient substrate radical is a crucial element in controlling the efficiency of activated OH rebound.
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影响因子：
4.9
作者：
Cryle, MJ;De Voss, JJ
通讯作者：
De Voss, JJ
影响因子：
15
作者：
Grant, Job L.;Hsieh, Chun H.;Makris, Thomas M.
通讯作者：
Makris, Thomas M.
影响因子：
16.6
作者：
Austin, Rachel N.;Luddy, Kate;Groves, John T.
通讯作者：
Groves, John T.
P450 OleT(JE)的分子基础：底物结合机制和主要途径的研究
影响因子：
3.5
作者：
Du, Juan;Liu, Lin;Yang, Jian Ming
通讯作者：
Yang, Jian Ming
DOI：
10.1073/pnas.90.6.2486
发表时间：
1993-03-15
影响因子：
11.1
作者：
FOX, BG;SHANKLIN, J;MUNCK, E
通讯作者：
MUNCK, E