Catalytic Alkylation Using a Cyclic S-Adenosylmethionine Regeneration System
Catalytic Alkylation Using a Cyclic S-Adenosylmethionine Regeneration System
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DOI：
10.1002/anie.201611038
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发表时间：
2017-03-27
影响因子：
16.6
通讯作者：
Andexer, Jennifer N.
中科院分区：
文献类型：
--
作者：
Mordhorst, Silja;Siegrist, Jutta;Andexer, Jennifer N.
S-腺苷甲硫氨酸依赖性甲基转移酶是许多化合物（如药物）的特异性烷基化的通用工具，但由于缺乏辅因子再生系统，它们的生物催化应用受到严重限制。我们报告了一个仿生的，多磷酸盐为基础的，甲基转移酶的环状级联。除了要甲基化的底物外，只需添加化学计量的甲硫氨酸和多磷酸盐。该系统相对于辅因子前体腺苷在所选底物的甲基化和乙基化反应中起催化作用，如HPLC分析所示。此外，进行H-1和C-13 NMR测量以明确鉴定甲硫氨酸为甲基供体，并深入了解反应的选择性。该系统构成了甲基转移酶的经济和环境友好应用的发展的重要阶段。
S-Adenosylmethionine-dependent methyltransferases are versatile tools for the specific alkylation of many compounds, such as pharmaceuticals, but their biocatalytic application is severely limited owing to the lack of a cofactor regeneration system. We report a biomimetic, polyphosphate-based, cyclic cascade for methyltransferases. In addition to the substrate to be methylated, only methionine and polyphosphate have to be added in stoichiometric amounts. The system acts catalytically with respect to the cofactor precursor adenosine in methylation and ethylation reactions of selected substrates, as shown by HPLC analysis. Furthermore, H-1 and C-13 NMR measurements were performed to unequivocally identify methionine as the methyl donor and to gain insight into the selectivity of the reactions. This system constitutes a vital stage in the development of economical and environmentally friendly applications of methyltransferases.