BesC Initiates C-C Cleavage through a Substrate-Triggered and Reactive Diferric-Peroxo Intermediate.
BesC Initiates C-C Cleavage through a Substrate-Triggered and Reactive Diferric-Peroxo Intermediate.
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DOI：
10.1021/jacs.1c11109
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发表时间：
2021-12-22
影响因子：
15
通讯作者：
Makris TM
中科院分区：
文献类型：
--
作者：
Manley OM;Tang H;Xue S;Guo Y;Chang WC;Makris TM
BESC催化依赖于铁和氧气的4-氯-L赖氨酸裂解生成4-氯-L-烯丙基甘氨酸、甲醛和氨。这一过程是生物合成途径的关键一步，该途径产生末端炔基氨基酸，可作为有用的生物正交柄用于蛋白质标记。作为一个新兴的双铁酶家族的成员，其典型特征是其血红素加氧酶样折叠和一组非常相似的配位配体，最近被称为HDOS，BESC执行一种不寻常的碳-碳切割反应，这与典型的双核-铁酶催化的反应有很大的不同。在这里，我们展示了BESC以底物门控的方式激活O2来产生二铁过氧中间体。对过氧基中间体与一系列赖氨酸衍生物的反应性的研究表明，BESC通过裂解C4-H键启动了这一独特的反应轨迹；这一过程代表了单一周转反应中的限速步骤。观察到的BESC的反应活性代表了双核铁酶的第一个例子，它利用二铁过氧基中间体能够裂解C-H键，作为其天然功能的一部分，从而绕过了高价中间体的形成，这种中间体更常与底物单加氧有关。
BesC catalyzes the iron- and O2-dependent cleavage of 4-chloro-l-lysine to form 4-chloro-l-allylglycine, formaldehyde, and ammonia. This process is a critical step for a biosynthetic pathway that generates a terminal alkyne amino acid which can be leveraged as a useful bio-orthogonal handle for protein labeling. As a member of an emerging family of diiron enzymes that are typified by their heme oxygenase-like fold and a very similar set of coordinating ligands, recently termed HDOs, BesC performs an unusual type of carbon–carbon cleavage reaction that is a significant departure from reactions catalyzed by canonical dinuclear-iron enzymes. Here, we show that BesC activates O2 in a substrate-gated manner to generate a diferric-peroxo intermediate. Examination of the reactivity of the peroxo intermediate with a series of lysine derivatives demonstrates that BesC initiates this unique reaction trajectory via cleavage of the C4–H bond; this process represents the rate-limiting step in a single turnover reaction. The observed reactivity of BesC represents the first example of a dinuclear-iron enzyme that utilizes a diferric-peroxo intermediate to capably cleave a C–H bond as part of its native function, thus circumventing the formation of a high-valent intermediate more commonly associated with substrate monooxygenations.
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影响因子：
15
作者：
Makris, Thomas M.;Vu, Van V.;Meier, Katlyn K.;Komor, Anna J.;Rivard, Brent S.;Muenck, Eckard;Que, Lawrence, Jr.;Lipscomb, John D.
通讯作者：
Lipscomb, John D.
甲烷酶氧化甲醇的酶促氧化中的关键物种的结构。
影响因子：
64.8
作者：
Banerjee, Rahul;Proshlyakov, Yegor;Lipscomb, John D.;Proshlyakov, Denis A.
通讯作者：
Proshlyakov, Denis A.
DOI：
10.1073/pnas.2015931118
发表时间：
2021-01-26
影响因子：
11.1
作者：
McBride MJ;Pope SR;Hu K;Okafor CD;Balskus EP;Bollinger JM Jr;Boal AK
通讯作者：
Boal AK
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：
15
作者：
Beauvais, LG;Lippard, SJ
通讯作者：
Lippard, SJ