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Updated: Jul 21, 2025

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Biocatalytic Fluoroalkylation Using Fluorinated S-Adenosyl-l-methionine Cofactors
Wenping Ding1,2, Minqi Zhou3,4, Huayu Li2
1Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.
Abstract:
Modification of organic molecules with fluorine functionalities offers a critical approach to develop new pharmaceuticals. Here, we report a multienzyme strategy for biocatalytic fluoroalkylation using S-adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) and fluorinated SAM cofactors prepared from ATP and fluorinated l-methionine analogues by an engineered human methionine adenosyltransferase hMAT2AI322A. This work introduces the first example of biocatalytic 3,3-difluoroallylation. Importantly, this strategy can be applied to late-stage site-selective fluoroalkylation of complex molecule vancomycin with conversions up to 99%.
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