A widespread family of ribosomal peptide metallophores involved in bacterial adaptation to metal stress - Archive ouverte HAL
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2024

A widespread family of ribosomal peptide metallophores involved in bacterial adaptation to metal stress

Sophie Jünger
  • Fonction : Auteur
Guy Lippens
Céline Guillaume
  • Fonction : Auteur
Lydie Oliveira
  • Fonction : Auteur
Enrico Falcone
Emiliano de Santis
Alex Rivera-Millot
  • Fonction : Auteur
Francesco Stellato
Céline Henry
Séverine Zirah
  • Fonction : Auteur
Svetlana Dubiley
Yanyan Li

Résumé

Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a structurally diverse group of natural products that bacteria employ in their survival strategies. Herein, we characterized the structure, the biosynthetic pathway, and the mode of action of a RiPP family called bufferins. With thousands of homologous biosynthetic gene clusters throughout the bacterial phylogenetic tree, bufferins form by far the largest family of RiPPs modified by multinuclear nonheme iron-dependent oxidases (MNIO, DUF692 family). Using Caulobacter vibrioides bufferins as a model, we showed that the conserved Cys residues of their precursors are transformed into 5-thiooxazoles, further expanding the reaction range of MNIO enzymes. This rare modification is installed in conjunction with a partner protein of the DUF2063 family. Bufferin precursors are rare examples of bacterial RiPPs found to feature an N-terminal Sec signal peptide allowing them to be exported by the ubiquitous Sec pathway. We reveal that bufferins are involved in copper homeostasis, and their metal-binding propensity requires the thiooxazole heterocycles. Bufferins enhance bacterial growth under copper stress by complexing excess metal ions. Our study thus describes a large family of RiPP metallophores and unveils a widespread but overlooked metal homeostasis mechanism in bacteria.
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Dates et versions

hal-04811059 , version 1 (29-11-2024)

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Citer

Laura Leprevost, Sophie Jünger, Guy Lippens, Céline Guillaume, Giuseppe Sicoli, et al.. A widespread family of ribosomal peptide metallophores involved in bacterial adaptation to metal stress. Proceedings of the National Academy of Sciences of the United States of America, 2024, 121 (49), pp.e2408304121. ⟨10.1073/pnas.2408304121⟩. ⟨hal-04811059⟩
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