AI Article Synopsis

  • Actinobacteria produce important antibiotics and metabolites for medicine and agriculture, with their production often controlled by diffusible hormones.
  • The study focuses on the binding of a specific hormone (AHFCA) to the transcriptional repressor MmfR in Streptomyces coelicolor, revealing key structural insights through X-ray crystallography.
  • Additionally, the research describes how hormone binding leads to DNA release, detailing the role of specific amino acids and functional groups, which can aid in the development of new antibiotics and applications in synthetic biology.

Article Abstract

Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear. 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 MmfR. 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.

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Source
http://dx.doi.org/10.1038/s41586-021-03195-xDOI Listing

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