Methyltransferase directed labeling of biomolecules and its applications

Methyltransferases (MTases) compose a large family of enzymes which have the ability to methylate a diverse set of targets, ranging from the three major biopolymers DNA, RNA and protein to small molecules. Most of these MTases use the cofactor S-Adenosyl-L-Methionine (AdoMet) as their methyl source. Given the important biological role of methylation, e.g. in epigenetic regulation of gene activity and the vast potential of targeted functionalization in biology, diagnostics and nanotechnology, it should come as no surprise that recent years have seen significant efforts in the development of AdoMet analogues with the aim of transferring moieties other than simple methyl groups. Two major classes of AdoMet analogues currently exist- the doubly-activated and aziridine based molecules- each of which employs a different approach for transalkylation, as opposed to transmethylation, of the target molecule. In this review, we discuss the various strategies for labelling and functionalizing biomolecules using AdoMet-dependent MTases and AdoMet analogues. We cover the synthetic routes to AdoMet analogues, their stability in biological environments and their application in transalkylation reactions. Finally, some perspectives are presented for the potential use of AdoMet analogues in biology research, (epi)genetics and nanotechnology.