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A ribosomally synthesised and post-translationally modified peptide containing a β-enamino acid and a macrocyclic motif

Author

Listed:
  • Shan Wang

    (University of Aberdeen)

  • Sixing Lin

    (Wuhan University)

  • Qing Fang

    (University of Aberdeen)

  • Roland Gyampoh

    (University of Ghana)

  • Zhou Lu

    (University of Aberdeen)

  • Yingli Gao

    (University of Aberdeen
    Jiangsu Ocean University)

  • David J. Clarke

    (University of Edinburgh)

  • Kewen Wu

    (University of Aberdeen)

  • Laurent Trembleau

    (University of Aberdeen)

  • Yi Yu

    (Wuhan University)

  • Kwaku Kyeremeh

    (University of Ghana)

  • Bruce F. Milne

    (University of Aberdeen
    University of Coimbra)

  • Jioji Tabudravu

    (University of Central Lancashire)

  • Hai Deng

    (University of Aberdeen)

Abstract

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally complex natural products with diverse bioactivities. Here we report discovery of a RiPP, kintamdin, for which the structure is determined through spectroscopy, spectrometry and genomic analysis to feature a bis-thioether macrocyclic ring and a β-enamino acid residue. Biosynthetic investigation demonstrated that its pathway relies on four dedicated proteins: phosphotransferase KinD, Lyase KinC, kinase homolog KinH and flavoprotein KinI, which share low homologues to enzymes known in other RiPP biosynthesis. During the posttranslational modifications, KinCD is responsible for the formation of the characteristic dehydroamino acid residues including the β-enamino acid residue, followed by oxidative decarboxylation on the C-terminal Cys and subsequent cyclization to provide the bis-thioether ring moiety mediated by coordinated action of KinH and KinI. Finally, conserved genomic investigation allows further identification of two kintamdin-like peptides among the kin-like BGCs, suggesting the occurrence of RiPPs from actinobacteria.

Suggested Citation

  • Shan Wang & Sixing Lin & Qing Fang & Roland Gyampoh & Zhou Lu & Yingli Gao & David J. Clarke & Kewen Wu & Laurent Trembleau & Yi Yu & Kwaku Kyeremeh & Bruce F. Milne & Jioji Tabudravu & Hai Deng, 2022. "A ribosomally synthesised and post-translationally modified peptide containing a β-enamino acid and a macrocyclic motif," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32774-3
    DOI: 10.1038/s41467-022-32774-3
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    1. Yu Imai & Kirsten J. Meyer & Akira Iinishi & Quentin Favre-Godal & Robert Green & Sylvie Manuse & Mariaelena Caboni & Miho Mori & Samantha Niles & Meghan Ghiglieri & Chandrashekhar Honrao & Xiaoyu Ma , 2019. "A new antibiotic selectively kills Gram-negative pathogens," Nature, Nature, vol. 576(7787), pages 459-464, December.
    2. Manuel A. Ortega & Yue Hao & Qi Zhang & Mark C. Walker & Wilfred A. van der Donk & Satish K. Nair, 2015. "Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB," Nature, Nature, vol. 517(7535), pages 509-512, January.
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    1. Wan-Qiu Liu & Xiangyang Ji & Fang Ba & Yufei Zhang & Huiling Xu & Shuhui Huang & Xiao Zheng & Yifan Liu & Shengjie Ling & Michael C. Jewett & Jian Li, 2024. "Cell-free biosynthesis and engineering of ribosomally synthesized lanthipeptides," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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