6U18
Directed evolution of a biosensor selective for the macrolide antibiotic clarithromycin
Summary for 6U18
| Entry DOI | 10.2210/pdb6u18/pdb |
| Descriptor | Erythromycin resistance repressor protein, CLARITHROMYCIN, CITRATE ANION, ... (4 entities in total) |
| Functional Keywords | macrolide, biosensor, dna-binding, dna binding protein-antibiotic complex, dna binding protein/antibiotic |
| Biological source | Escherichia coli |
| Total number of polymer chains | 2 |
| Total formula weight | 44888.96 |
| Authors | Li, Y.,Reed, M.,Wright, H.T.,Cropp, T.A.,Williams, G. (deposition date: 2019-08-15, release date: 2020-08-19, Last modification date: 2023-10-11) |
| Primary citation | 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 Cited by 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: 34546703DOI: 10.1021/acssynbio.1c00151 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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