S-adenosylhomocysteine as a methyl transfer catalyst in biocatalytic methylation reactions
S-adenosylhomocysteine as a methyl transfer catalyst in biocatalytic methylation reactions
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DOI：
10.1038/s41929-019-0300-0
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发表时间：
2019-08-01
期刊：
影响因子：
37.8
通讯作者：
Seebeck, Florian P.
中科院分区：
文献类型：
--
作者：
Liao, Cangsong;Seebeck, Florian P.
S-腺苷甲硫氨酸依赖性甲基转移酶是一类能催化复杂天然产物区域、化学和立体特异性甲基化的酶。这些酶可能是非常有用的工具，化学酶的生产和多样化的天然或人工化合物。尽管有这种潜力，甲基转移酶的体外应用受到限制，它们需要S-腺苷甲硫氨酸作为化学计量的甲基供体。该试剂的化学复杂性、不稳定性、高成本和差的原子经济性阻止了制备性体外甲基化反应成为天然产物研究中的常规方案和工艺开发的可行选择。在这篇文章中，我们证明，C-，N-和O-特异性甲基转移酶可以与卤化物甲基转移酶相结合，形成酶级联，只需要催化浓度的S-腺苷甲硫氨酸和使用甲基碘作为化学计量的甲基供体。
S-adenosylmethionine-dependent methyltransferases form a large family of enzymes that can catalyse regio-, chemo- and stereospecific methylation of complex natural products. These enzymes could be very useful tools for the chemoenzymatic production and diversification of natural or artificial compounds. Despite this potential, in vitro applications of methyltransferases are limited by their requirement for S-adenosylmethionine as a stoichiometric methyl donor. The chemical complexity, instability, high cost and poor atom economy of this reagent prevent preparative in vitro methylation reactions from becoming routine protocols in natural product research and viable options for process development. In this Article we demonstrate that C-, N- and O-specific methyltransferases can be combined with halide methyltransferases to form enzyme cascades that require only catalytic concentrations of S-adenosylmethionine and use methyl iodide as the stoichiometric methyl donor.