Bennett Matthew R, Shepherd Sarah A, Cronin Victoria A, Micklefield Jason
School of Chemistry & Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
School of Chemistry & Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
Curr Opin Chem Biol. 2017 Apr;37:97-106. doi: 10.1016/j.cbpa.2017.01.020. Epub 2017 Mar 2.
S-adenosyl-L-methionine-dependent methyltransferses are ubiquitous in nature, methylating a vast range of small molecule metabolites, as well as biopolymers. This review covers the recent advances in the development of methyltransferase enzymes for synthetic applications, focusing on the methyltransferase catalyzed transformations with S-adenosyl methionine analogs, as well as non-native substrates. We discuss how metabolic engineering approaches have been used to enhance S-adenosyl methionine production in vivo. Enzymatic approaches that enable the more efficient generation of S-adenosyl methionine analogs, including more stable analogs, will also be described; this has expanded the biocatalytic repertoire of methyltransferases from methylation to a broader range of alkylation reactions. The review also examines how the selectivity of the methyltransferase enzymes can be improved through structure guided mutagenesis approaches. Finally, we will discuss how methyltransferases can be deployed in multi-enzyme cascade reactions and suggest future challenges and avenues for further investigation.
S-腺苷-L-甲硫氨酸依赖性甲基转移酶在自然界中广泛存在，可将多种小分子代谢物以及生物聚合物甲基化。本综述涵盖了用于合成应用的甲基转移酶的最新进展，重点关注甲基转移酶催化的与S-腺苷甲硫氨酸类似物以及非天然底物的转化反应。我们讨论了代谢工程方法如何用于提高体内S-腺苷甲硫氨酸的产量。还将描述能够更高效生成S-腺苷甲硫氨酸类似物（包括更稳定的类似物）的酶促方法；这已将甲基转移酶的生物催化范围从甲基化扩展到更广泛的烷基化反应。本综述还研究了如何通过结构导向诱变方法提高甲基转移酶的选择性。最后，我们将讨论甲基转移酶如何应用于多酶级联反应，并提出未来的挑战和进一步研究的方向。
