Elucidation of divergent desaturation pathways in the formation of vinyl isonitrile and isocyanoacrylate.
Elucidation of divergent desaturation pathways in the formation of vinyl isonitrile and isocyanoacrylate.
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DOI：
10.1038/s41467-022-32870-4
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发表时间：
2022-09-12
影响因子：
16.6
通讯作者：
Chang, Wei-Chen
中科院分区：
文献类型：
--
作者：
Kim, Wantae;Chen, Tzu-Yu;Cha, Lide;Zhou, Grace;Xing, Kristi;Canty, Nicholas Koenig;Zhang, Yan;Chang, Wei-Chen
铁和2-酮戊二酸依赖性（Fe/2 OG）酶采用两种不同类型的去饱和作用来构建在含异腈的天然产物中发现的乙烯基异腈和异氰基丙烯酸酯部分。底物结合的蛋白质结构揭示了一个合理的策略，影响去饱和，并暗示这些酶的底物混杂。合成类似物并用作机制探针以验证结构观察。代替如先前提出的通过羟基化中间体进行，利用合理的碳阳离子物质来触发C=C键安装。这些Fe/2 OG酶还可以容纳具有相反手性和不同官能团的类似物，包括异腈-（D）-酪氨酸、N-甲酰基酪氨酸和根皮酸，同时保持反应选择性。虽然典型的氧反弹途径已被几种Fe/2 OG酶所利用，但对去饱和过程的了解仍有待阐明。在这里，作者认为，碳正离子可能会被部署，使化学分歧去饱和通过脱羧和去质子化。
Two different types of desaturations are employed by iron- and 2-oxoglutarate-dependent (Fe/2OG) enzymes to construct vinyl isonitrile and isocyanoacrylate moieties found in isonitrile-containing natural products. A substrate-bound protein structure reveals a plausible strategy to affect desaturation and hints at substrate promiscuity of these enzymes. Analogs are synthesized and used as mechanistic probes to validate structural observations. Instead of proceeding through hydroxylated intermediate as previously proposed, a plausible carbocation species is utilized to trigger C=C bond installation. These Fe/2OG enzymes can also accommodate analogs with opposite chirality and different functional groups including isonitrile-(D)-tyrosine, N-formyl tyrosine, and phloretic acid, while maintaining the reaction selectivity. While canonical oxygen-rebound pathway has been utilized by several Fe/2OG enzymes, insights into the desaturation process remain to be elucidated. Here, the authors suggest that a carbocation might be deployed to enable chemically divergent desaturations through decarboxylation and deprotonation.
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影响因子：
15
作者：
Dunham NP;Chang WC;Mitchell AJ;Martinie RJ;Zhang B;Bergman JA;Rajakovich LJ;Wang B;Silakov A;Krebs C;Boal AK;Bollinger JM Jr
通讯作者：
Bollinger JM Jr
影响因子：
11.9
作者：
Hohlman RM;Sherman DH
通讯作者：
Sherman DH
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
16.6
作者：
Brady, SF;Clardy, J
通讯作者：
Clardy, J
双核羰基铁配合物中三氟甲基异氰配体的偶联
影响因子：
1.9
作者：
Li, Guoliang;Liu, Lihua;King, R. Bruce
通讯作者：
King, R. Bruce