一种混杂的细胞色素 P450 羟化酶可羟化芳香 2,5-二酮哌嗪的脂肪族和芳香族 C-H 键。
A Promiscuous Cytochrome P450 Hydroxylates Aliphatic and Aromatic C-H Bonds of Aromatic 2,5-Diketopiperazines.
机构信息
Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, FL, 32610, USA.
Department of Plant Pathology, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, 32611, USA.
出版信息
Chembiochem. 2019 Apr 15;20(8):1068-1077. doi: 10.1002/cbic.201800736. Epub 2019 Mar 27.
Cytochrome P450 enzymes generally functionalize inert C-H bonds, and thus, they are important biocatalysts for chemical synthesis. However, enzymes that catalyze both aliphatic and aromatic hydroxylation in the same biotransformation process have rarely been reported. A recent biochemical study demonstrated the P450 TxtC for the biosynthesis of herbicidal thaxtomins as the first example of this unique type of enzyme. Herein, the detailed characterization of substrate requirements and biocatalytic applications of TxtC are reported. The results reveal the importance of N-methylation of the thaxtomin diketopiperazine (DKP) core on enzyme reactions and demonstrate the tolerance of the enzyme to modifications on the indole and phenyl moieties of its substrates. Furthermore, hydroxylated, methylated, aromatic DKPs are synthesized through a biocatalytic route comprising TxtC and the promiscuous N-methyltransferase Amir_4628; thus providing a basis for the broad application of this unique P450.
细胞色素 P450 酶通常使惰性 C-H 键官能化，因此，它们是化学合成的重要生物催化剂。然而，在同一生物转化过程中催化脂肪族和芳香族羟化的酶很少有报道。最近的一项生化研究表明，P450 TxtC 是除草剂 thaxtomin 的生物合成酶，这是这种独特酶类型的首例。本文报道了 TxtC 的底物要求和生物催化应用的详细特征。结果表明 thaxtomin 二酮哌嗪 (DKP) 核心的 N-甲基化对酶反应很重要，并证明了该酶对其底物吲哚和苯部分修饰的耐受性。此外，通过包含 TxtC 和混杂的 N-甲基转移酶 Amir_4628 的生物催化途径合成了羟化、甲基化、芳香族 DKP，从而为该独特 P450 的广泛应用提供了基础。
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