Decarboxylation of Fatty Acids to Terminal Alkenes by Cytochrome P450 Compound I
Decarboxylation of Fatty Acids to Terminal Alkenes by Cytochrome P450 Compound I
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DOI：
10.1021/jacs.5b01965
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发表时间：
2015-04-22
影响因子：
15
通讯作者：
Makris, Thomas M.
中科院分区：
文献类型：
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作者：
Grant, Job L.;Hsieh, Chun H.;Makris, Thomas M.
OleT(JE) 是一种细胞色素 P450，使用过氧化氢作为共底物催化脂肪酸转化为末端烯烃。对二十烷酸底物的分析研究表明，该酶主要生成十九碳烯，并且二氧化碳是该反应的一种碳副产物。将过氧化氢添加到氘化底物-酶 (E-S) 复合物中会导致铁 (IV) 氧代阳离子自由基（化合物 I）中间体的瞬时形成，该中间体在光谱上与进行氧插入化学的中间体无法区分。化合物 I 衰变的动力学同位素效应表明它提取底物氢原子以引发脂肪酸脱羧。总之，这些结果表明，烯烃形成的初始机制不是由氧反弹引起的，与广泛建议的 P450 单氧化反应类似。
OleT(JE), a cytochrome P450, catalyzes the conversion of fatty acids to terminal alkenes using hydrogen peroxide as a cosubstrate. Analytical studies with an eicosanoic acid substrate show that the enzyme predominantly generates nonadecene and that carbon dioxide is the one carbon coproduct of the reaction. The addition of hydrogen peroxide to a deuterated substrate-enzyme (E-S) complex results in the transient formation of an iron(IV) oxo p cation radical (Compound I) intermediate which is spectroscopically indistinguishable from those that perform oxygen insertion chemistries. A kinetic isotope effect for Compound I decay suggests that it abstracts a substrate hydrogen atom to initiate fatty acid decarboxylation. Together, these results indicate that the initial mechanism for alkene formation, which does not result from oxygen rebound, is similar to that widely suggested for P450 monooxygenation reactions.