Methylation of DNA cytosines or adenines, RNA adenines or riboses, histone amino acids are pivotal epigenetic mechanisms that are paramount importance for various biological processes including mammalian embryonic development, normal regulation of transcription, chromatin structure, disease pathogenesis and other. Aberrations in the methylation mechanisms usually cause cellular processes dysregulations which usually provoke human diseases such as neurodegenerative disorders, cancer and others [1, 2].
A large family of S-adenosyl-L-methionine (AdoMet)-depended methyltransferases (MTases) catalyzes the enzymatic methylation mechanism. These enzymes are widely used as a biotechnological tool for biomolecules such as DNA, RNA, proteins or small molecules specific targeting to deciphering epigenetic or biological processes and their regulation. Moreover, methyltransferases are used as a tool for chemoenzymatic production of small compounds such as pharmaceutical, vanillin or artificial compounds [3, 4]. To pave the way for a broader utilization of MTases in area of chemical and synthetic biology to produce various compounds we used halide methyltransferases (HMT) for deeper analysis of enzymatic parameters and HMT-based system for AdoMet cofactor synthesis. We analyzed HMT enzymes from different organisms and off-the-shelf reagent methyl iodide for chemoenzymatic synthesis of cofactor AdoMet. Furthermore, we showed that HMT-based system in enzyme cascades with various DNA methyltransferases could be used for specific DNA targets methylation. We proposed that wider utilization of promiscuous HMT could broaden a high-throughput approaches for chemoenzymatic synthesis of AdoMet cofactors in vitro or even in vivo.