6U18

Directed evolution of a biosensor selective for the macrolide antibiotic clarithromycin

6U18 の概要

• エントリーDOI: 10.2210/pdb6u18/pdb
• 分子名称: Erythromycin resistance repressor protein, CLARITHROMYCIN, CITRATE ANION, ... (4 entities in total)
• 機能のキーワード: macrolide, biosensor, dna-binding, dna binding protein-antibiotic complex, dna binding protein/antibiotic
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44888.96

構造登録者

Li, Y.,Reed, M.,Wright, H.T.,Cropp, T.A.,Williams, G. (登録日: 2019-08-15, 公開日: 2020-08-19, 最終更新日: 2023-10-11)

主引用文献

Li, Y.,Reed, M.,Wright, H.T.,Cropp, T.A.,Williams, G.J.
Development of Genetically Encoded Biosensors for Reporting the Methyltransferase-Dependent Biosynthesis of Semisynthetic Macrolide Antibiotics.
Acs Synth Biol, 2021

PubMed 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 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.

PubMed: 34546703
DOI: 10.1021/acssynbio.1c00151

実験手法

X-RAY DIFFRACTION (2 Å)