School of Chemistry, The University of Manchester, UK.
Chembiochem. 2012 Dec 21;13(18):2642-55. doi: 10.1002/cbic.201200556. Epub 2012 Nov 23.
S-adenosyl methionine (SAM) is a universal biological cofactor that is found in all branches of life where it plays a critical role in the transfer of methyl groups to various biomolecules, including DNA, proteins and small-molecule secondary metabolites. The methylation process thus has important implications in various disease processes and applications in industrial chemical processing. This methyl transfer is catalysed by SAM-dependent methyltransferases (MTases), which are by far the largest groups of SAM-dependent enzymes. A significant amount is now known regarding the structural biology and enzymology of these enzymes, and, consequently, there is now significant scope for the development of new MTases and SAM analogues for applications from biomolecular imaging to biocatalytic industrial processes. This review will focus on current efforts in the manipulation of class I and V SAM-dependent MTases and the use of synthetic SAM analogues, which together offer the best prospects for rational redesign towards biotechnological applications. Firstly, metabolic engineering of organisms incorporating small-molecule MTases is discussed; this can be applied in a variety of areas from the industrial bioprocessing of flavourants and antibiotics to frontier research in biofuel production and bioremediation. Secondly, the application of MTases in combination with SAM analogues is reviewed; this allows the tagging of proteins and oligonucleotides with moieties other than the methyl group. Such tagging allows the isolation of the tagged biomolecule and aids its visualisation by a range of analytical methods. The review then summarises the potential advantages of MTase-mediated chemistry and offers some future perspectives on downstream applications.
S-腺苷甲硫氨酸（SAM）是一种普遍存在于所有生命分支中的生物辅酶，它在将甲基基团转移到各种生物分子（包括 DNA、蛋白质和小分子次生代谢物）中起着关键作用。因此，甲基化过程在各种疾病过程中具有重要意义，并且在工业化学加工中有广泛的应用。这种甲基转移由依赖 SAM 的甲基转移酶（MTases）催化，这些酶是迄今为止最大的依赖 SAM 的酶组之一。目前已经对这些酶的结构生物学和酶学有了大量的了解，因此现在有很大的空间可以开发新的 MTases 和 SAM 类似物，从生物分子成像到生物催化工业过程的应用都有很大的发展前景。这篇综述将集中讨论目前对 I 类和 V 类依赖 SAM 的 MTases 的操纵以及合成 SAM 类似物的应用，这两者共同为基于理性设计的生物技术应用提供了最好的前景。首先，讨论了包含小分子 MTases 的生物体的代谢工程；这可以应用于各种领域，从风味剂和抗生素的工业生物加工到前沿的生物燃料生产和生物修复研究。其次，综述了 MTases 与 SAM 类似物联合应用；这允许用除甲基以外的基团对蛋白质和寡核苷酸进行标记。这种标记可以分离标记的生物分子，并通过一系列分析方法帮助其可视化。然后，该综述总结了 MTase 介导的化学的潜在优势，并对下游应用提供了一些未来的展望。
