A Promiscuous Cytochrome P450 Hydroxylates Aliphatic and Aromatic C-H Bonds of Aromatic 2,5-Diketopiperazines.
A Promiscuous Cytochrome P450 Hydroxylates Aliphatic and Aromatic C-H Bonds of Aromatic 2,5-Diketopiperazines.
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DOI：
10.1002/cbic.201800736
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发表时间：
2019-04-15
期刊：
影响因子：
--
通讯作者：
Ding Y
中科院分区：
文献类型：
--
作者：
Jiang G;Zhang Y;Powell MM;Hylton SM;Hiller NW;Loria R;Ding Y
细胞色素P450酶一般作用于惰性C-H键，使其成为化学合成的重要生物催化剂。然而，在同一生物转化过程中同时催化脂肪族和芳香族羟基化的酶还很少有报道。我们最近的生化研究证明了用于生物合成除草剂泰素的P450 TxtC是这种独特类型的酶的第一个例子。在此，我们报告了TxtC的底物需求和生物催化应用的详细表征。我们的结果揭示了泰索霉素二酮哌嗪(DKP)核心的N-甲基化在酶反应中的重要性，并证明了酶对其底物的吲哚和苯基部分的修饰的耐受性。此外，本工作通过生物催化路线合成了羟基化、甲基化的芳香族DKPs，包括TxtC和混杂的N-甲基转移酶(MT)AMIR_4628，为这一独特的P450的广泛应用奠定了基础。酶促脂肪族和芳香族羟基化：P450TxtC对除草剂二酮并哌嗪泰素D的脂肪族和芳香族羟基化反应是独一无二的。
Cytochrome P450 enzymes generally functionalize the inert C-H bonds, making them important biocatalysts for chemical synthesis. However, enzymes that catalyze both aliphatic and aromatic hydroxylation in the same biotransformation process have rarely been reported. Our recent biochemical study demonstrated the P450 TxtC for the biosynthesis of herbicidal thaxtomins as the first example of this unique type of enzymes. Herein, we report the detailed characterization of substrate requirement and biocatalytic application of TxtC. Our results reveal the importance of N-methylations of the thaxtomin diketopiperazine (DKP) core on enzyme reactions and demonstrate the enzyme tolerance to modifications on the indole and phenyl moieties of its substrates. Furthermore, this work synthesizes hydroxylated, methylated aromatic DKPs in a biocatalytic route comprising TxtC and the promiscuous N-methyltransferase (MT) Amir_4628, laying the basis for the broad application of this unique P450. Enzymatic aliphatic and aromatic hydroxylation: The P450 TxtC is unique for both aliphatic and aromatic hydroxylation on herbicidal diketopiperazine thaxtomin D. This study revealed the substrate scope, reaction promiscuity and biocatalytic application of this synthetically valuable enzyme.
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影响因子：
14.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0805983105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Cryle, Max J.;Schlichting, Ilme
通讯作者：
Schlichting, Ilme
影响因子：
4.4
作者：
Jiang, Guangde;Zhang, Yucheng;Ding, Yousong
通讯作者：
Ding, Yousong
影响因子：
2.9
作者：
Giessen, Tobias W.;von Tesmar, Alexander M.;Marahiel, Mohamed A.
通讯作者：
Marahiel, Mohamed A.
影响因子：
3.2
作者：
Healy, FG;Krasnoff, SB;Loria, R
通讯作者：
Loria, R