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Molecular basis for control of antibiotic production by a bacterial hormone
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Zhou, Shanshan, Bhukya, Hussain, Malet, Nicolas, Harrison, Peter J. , Rea, Dean, Belousoff, Matthew J., Venugopal, Hariprasad, Sydor, Paulina K., Styles, Kathryn, Song, Lijiang, Cryle, Max J., Alkhalaf, Lona M., Fülöp, Vilmos, Challis, Gregory L. and Corre, Christophe (2021) Molecular basis for control of antibiotic production by a bacterial hormone. Nature, 590 (7846). pp. 463-467. doi:10.1038/s41586-021-03195-x ISSN 0028-0836.
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Official URL: http://dx.doi.org/10.1038/s41586-021-03195-x
Abstract
Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture1. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear2. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2) is initiated by the binding of 2-alkyl-4-hydroxymethylfuran-3-carboxylic acid (AHFCA) hormones to the TFTR MmfR3. Here we report the X-ray crystal structure of an MmfR–AHFCA complex, establishing the structural basis for hormone recognition. We also elucidate the mechanism for DNA release upon hormone binding through the single-particle cryo-electron microscopy structure of an MmfR–operator complex. DNA binding and release assays with MmfR mutants and synthetic AHFCA analogues define the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release. These findings will facilitate the exploitation of actinobacterial hormones and their associated TFTRs in synthetic biology and in the discovery of new antibiotics.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QR Microbiology | ||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) |
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| Library of Congress Subject Headings (LCSH): | Actinobacteria, Microbial biotechnology, Antibiotics -- Synthesis | ||||||||||||
| Journal or Publication Title: | Nature | ||||||||||||
| Publisher: | Nature Publishing | ||||||||||||
| ISSN: | 0028-0836 | ||||||||||||
| Official Date: | 18 February 2021 | ||||||||||||
| Dates: |
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| Volume: | 590 | ||||||||||||
| Number: | 7846 | ||||||||||||
| Page Range: | pp. 463-467 | ||||||||||||
| DOI: | 10.1038/s41586-021-03195-x | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||
| Date of first compliant deposit: | 11 February 2021 | ||||||||||||
| Date of first compliant Open Access: | 3 August 2021 | ||||||||||||
| RIOXX Funder/Project Grant: |
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