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Updated: Sep 18, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Nonnative Thiol and Aniline Methylation, Including Enantioselective Dithiol Desymmetrization, by Multicomponent
Amardeep Kumar1, Osman Ishag Adam1, Paras Gupta1
1Department of Chemistry, Indiana University, Bloomington, Indiana, USA.
Abstract:
Despite their potential synthetic utility, cobamide-dependent MTases are relatively underutilized for biocatalysis. We developed mixed MtaABC/MtgABC enzyme platforms capable of catalyzing methylation of non-native thiol and aniline substrates using unactivated methyl donors like methanol and glycine betaine. This approach allows highly enantioselective and site-selective methylation of aliphatic thiols with high turnover number (up to 6000), providing the first demonstration of enantioselective non-native catalysis by cobamide-dependent enzymes. The MtaAC+MtgB system was subsequently engineered through site-directed mutagenesis, resulting in large enhancements in activity for the desymmetrization of non-native ester-containing prochiral thiols. These findings establish MTase complexes as a promising platform for non-native biocatalysis.
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