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Updated: Oct 2, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Development of Genetically Encoded Biosensors for Reporting the Methyltransferase-Dependent Biosynthesis of
Yiwei Li1, Megan Reed2, H Tonie Wright3
1Department of Chemistry, NC State University, Raleigh, North Carolina 27695, United States.
Abstract:
Clarithromycin is an improved semisynthetic analogue of the naturally occurring macrolide, erythromycin. The subtle modification of a methyl group on the C-6 hydroxyl group endows the molecule with improved acid stability and results in a clinically useful antibiotic. Here, we show that the effector specificity of the biosensor protein, MphR, can be evolved to selectively recognize clarithromycin and therefore report on the production of this molecule in vivo. In addition, a crystal structure of the evolved variant reveals the molecular basis for selectivity and provides a guide for the evolution of a new metabolic function using this biosensor.
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