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.
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
TL;DR:
It is shown 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.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
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.