2021 journal article

Development of Genetically Encoded Biosensors for Reporting the Methyltransferase-Dependent Biosynthesis of Semisynthetic Macrolide Antibiotics

ACS Synthetic Biology, 10(10), 2520–2531.

By: Y. Li n, M. Reed*, H. Wright*, T. Cropp* & G. Williams n

co-author countries: United States of America 🇺🇸
author keywords: macrolide; polyketide; biosensor; transcription factor; synthetic biology
MeSH headings : Anti-Bacterial Agents / biosynthesis; Anti-Bacterial Agents / chemistry; Biosensing Techniques / methods; Macrolides / chemistry; Macrolides / metabolism; Methyltransferases / metabolism; Molecular Structure; Mutagenesis
Source: ORCID
Added: September 22, 2021

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.