Evidence for a 1,3-Dipolar Cyclo-addition Mechanism in the Decarboxylation of Phenylacrylic Acids Catalyzed by Ferulic Acid Decarboxylase
Evidence for a 1,3-Dipolar Cyclo-addition Mechanism in the Decarboxylation of Phenylacrylic Acids Catalyzed by Ferulic Acid Decarboxylase
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DOI：
10.1021/jacs.7b05060
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发表时间：
2017-08-16
影响因子：
15
通讯作者：
Marsh, E. Neil G.
中科院分区：
文献类型：
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作者：
Ferguson, Kyle L.;Eschweiler, Joseph D.;Marsh, E. Neil G.
阿魏酸脱羧酶利用一种新发现的辅助因子，烯酰化黄素单核苷酸（prFMN）催化苯丙烯酸的脱羧。所提出的机制涉及到一个假定的五环中间体的形成，该中间体是由prFMN与底物的α - β双键的1,3偶极环加成形成的，它用于激活底物的脱羧。然而，酶催化的1,3偶极环加成是前所未有的，其他机制似乎是可信的。在这里，我们描述了一种基于机理的抑制剂-2-氟-2-硝基乙烯苯的使用，以捕获假定的环加成中间体，从而证明prFMN可以在1,3偶极环加成反应中作为偶极子起作用，作为新型酶促反应的初始步骤。
Ferulic acid decarboxylase catalyzes the decarboxylation of phenylacrylic acid using a newly identified cofactor, prenylated flavin mononucleotide (prFMN). The proposed mechanism involves the formation of a putative pentacyclic intermediate formed by a 1,3 dipolar cyclo-addition of prFMN with the alpha-beta double bond of the substrate, which serves to activate the substrate toward decarboxylation. However, enzyme catalyzed 1,3 dipolar cyclo-additions are unprecedented and other mechanisms are plausible. Here we describe the use of a mechanism-based inhibitor, 2-fluoro-2-nitro-vinylbenzene, to trap the putative cyclo-addition intermediate, thereby demonstrating that prFMN can function as a dipole in a 1,3 dipolar cyclo-addition reaction as the initial step in a novel type of enzymatic reaction.