Abstract
Transferases have emerged as among the best catalysts for enzyme-mediated bioorthogonal functional group installation to advance innovative in vitro, cell-based and in vivo chemical biology applications. This review introduces the key considerations for selecting enzyme catalysts and chemoselective reactions most amenable to bioorthogonal platform development and highlights relevant key technology development and applications for one ubiquitous transferase subclass - methyltransferases (MTs). Within this context, recent advances in MT-enabled bioorthogonal labeling/conjugation relevant to DNA, RNA, protein, and natural products (i.e. complex small molecule metabolites) are highlighted.