Enantioselective intramolecular C-H amination catalyzed by engineered cytochrome P450 enzymes in vitro and in vivo.
Enantioselective intramolecular C-H amination catalyzed by engineered cytochrome P450 enzymes in vitro and in vivo.
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DOI：
10.1002/anie.201304401
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发表时间：
2013-08-26
影响因子：
16.6
通讯作者：
Arnold, Frances H.
中科院分区：
文献类型：
--
作者：
McIntosh, John A.;Coelho, Pedro S.;Farwell, Christopher C.;Wang, Z. Jane;Lewis, Jared C.;Brown, Tristan R.;Arnold, Frances H.
含铁单加氧酶在自然界中扮演着不同的角色，从烷烃羟基酶的初级代谢功能到细胞色素P450酶的异物解毒和次生代谢作用。[1]这些酶的共同之处是能够还原地激活分子氧以产生高度亲电的氧物种，其反应活性与“恶烯”(含六个价电子的氧原子)相当。[2]尤其是P450酶具有非凡的能力，可以在原本不活性的碳骨架中的几乎任何位置插入氧原子，导致在不同的天然产品中引入羟基或环氧化物功能。虽然酶能够将氧原子插入甚至未活化的C±H键，但氮原子可以被结合的位置受到更多的限制。例如，转氨酶、解氨酶和氨基酸脱氢酶[3]在反应过程中以氧化或其他化学活性碳原子为靶标。催化C±H键协同氧化胺化的酶显然不存在于S的化学催化剂库中。
Iron-containing monooxygenases play diverse roles in nature, which range from the primary metabolic functions of alkane hydroxylases to the xenobiotic detoxification and secondary metabolic roles of cytochrome P450 enzymes.[1] Common to these enzymes is the ability to reductively activate molecular oxygen to generate highly electrophilic oxygen species, whose reactivity is comparable with that of “oxenes”(oxygen atoms that contain six valence electrons).[2] P450 enzymes in particular possess the remarkable ability to insert oxygen atoms at virtually any position within otherwise unreactive carbon skeletons, leading to the introduction of hydroxy or epoxide functionalities in diverse natural products. Whereas enzymes are capable of inserting oxygen atoms into even unactivated CÀH bonds, the sites into which nitrogen atoms can be incorporated are more constrained. Transaminases, ammonia lyases, and amino acid dehydrogenases, for example,[3] target oxidized or otherwise chemically activated carbon atoms during reaction. Enzymes that catalyze the concerted oxidative amination of CÀH bonds are apparently absent from nature s repertoire of chemical catalysts.
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影响因子：
11.9
作者：
Podust LM;Sherman DH
通讯作者：
Sherman DH
影响因子：
56.9
作者：
Coelho, Pedro S.;Brustad, Eric M.;Arnold, Frances H.
通讯作者：
Arnold, Frances H.
DOI：
10.1039/c39820001400
发表时间：
1982-01-01
影响因子：
--
作者：
BRESLOW, R;GELLMAN, SH
通讯作者：
GELLMAN, SH
影响因子：
56.9
作者：
DAWSON, JH
通讯作者：
DAWSON, JH
影响因子：
4.1
作者：
Pazmino, D. E. Torres;Winkler, M.;Fraaije, M. W.
通讯作者：
Fraaije, M. W.