Work

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

Year: 2021

Type: article

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.

Source: ACS Synthetic Biology

DOI: 10.1021/acssynbio.1c00151

Authors: Yiwei Li, Megan Reed, H. Tonie Wright, T. Ashton Cropp, Gavin J. Williams

Institutions: North Carolina State University, Virginia Commonwealth University

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: University of North Carolina, Virginia Commonwealth University, National Institutes of Health, National Institute of General Medical Sciences

Awards: G3382523617, X-ray Crystallographic Data Collection System, Designer biosensors for directed evolution of macrolide biosynthetic enzymes