{
  "abstract": "A significant challenge in addressing the antibiotic resistance crisis is identifying new antimicrobial compounds. Although natural products produced by fungi and bacteria, particularly actinomycetes, have been the source of most antibiotics discovered over the past 80 years, they have fallen out of favor due to the frequent rediscovery of known drug scaffolds. The current perception is that antibiotic-producing actinomycetes have been over-mined and possess little novelty left to yield. Here, we demonstrate that by using improved fractionation approaches that enrich previously overlooked minor products, even well-studied strains of antibiotic-producing actinomycetes can provide new chemical scaffolds with unique modes of action. By fractionating a library of natural product extracts from soil bacteria, we show that Streptomyces rimosus, the source of the well-known antibiotic oxytetracycline, produces a previously overlooked cyclic depsipeptide antibiotic that we called manikomycin. Manikomycin can kill multi-drug-resistant Enterobacteriaceae and is not susceptible to resistance associated with clinically used antibiotics. Biochemical, genetic, and structural analyses reveal that manikomycin binds in the 'exit' or E site of the large subunit of the bacterial ribosome preventing the entry of the 3' end of the tRNA into the E site and effectively hindering the translocation step of protein synthesis in a sequence context-specific manner. Manikomycin is the first antibacterial agent to target the critical but underexplored E site in the large ribosomal subunit, highlighting its value as a lead for developing new antibiotics.",
  "abstract_shown": true,
  "affiliations": [
    "David Braley Centre for Antibiotics Discovery, McMaster University, Hamilton, Ontario, Canada",
    "Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada",
    "M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada",
    "Center for Biomolecular Sciences, University of Illinois at Chicago, Chicago, IL, USA",
    "Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, USA",
    "Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany",
    "Center for Biomolecular Sciences, University of Illinois at Chicago, Chicago, IL, USA. shura@uic.edu",
    "Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, USA. shura@uic.edu",
    "Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany. daniel.wilson@uni-hamburg.de",
    "David Braley Centre for Antibiotics Discovery, McMaster University, Hamilton, Ontario, Canada. wrightge@mcmaster.ca",
    "Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. wrightge@mcmaster.ca",
    "M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada. wrightge@mcmaster.ca"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Manpreet Kaur",
      "orcid": "0000-0002-2506-0611"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Dmitrii Y. Travin",
      "orcid": "0000-0003-0189-0159"
    },
    {
      "affs": [
        5
      ],
      "name": "Max J. Berger",
      "orcid": "0009-0001-7093-9086"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Manoj Jangra",
      "orcid": "0000-0003-3423-7105"
    },
    {
      "affs": [
        5
      ],
      "name": "Martino Morici",
      "orcid": "0000-0002-7304-5264"
    },
    {
      "affs": [
        5
      ],
      "name": "Haaris Ahsan Safdari",
      "orcid": "0000-0003-3533-090X"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Dorota Klepacki"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Wenliang Wang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Michael A. Cook",
      "orcid": "0000-0001-7230-8678"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Sommer Chou",
      "orcid": "0000-0001-7742-7350"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Allison K. Guitor",
      "orcid": "0000-0002-6290-6233"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kalinka K. Koteva",
      "orcid": "0000-0002-6446-9567"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Min Xu",
      "orcid": "0000-0002-6661-5177"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Linda J. Ejim"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Aline Fiebig‐Comyn",
      "orcid": "0009-0009-0786-4331"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yeganeh Yousefi",
      "orcid": "0000-0002-4536-0873"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Brian K. Coombes",
      "orcid": "0000-0001-9883-1010"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lesley T. MacNeil",
      "orcid": "0000-0001-9562-8754"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Nora Vázquez‐Laslop",
      "orcid": "0000-0003-2256-693X"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Alexander S. Mankin",
      "orcid": "0000-0002-3301-827X"
    },
    {
      "affs": [
        8
      ],
      "name": "Daniel N. Wilson",
      "orcid": "0000-0003-3816-3828"
    },
    {
      "affs": [
        9,
        10,
        11
      ],
      "name": "Gerard D. Wright",
      "orcid": "0000-0002-9129-7131"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/44cq6attfaaqf.bib",
  "cited_by": 12,
  "doi": "10.1038/s41586-026-10589-2",
  "fulltext_url": null,
  "id": "44cq6attfaaqf",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-10589-2",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2736|Microbial Natural Products and Biosynthesis"
    ]
  ],
  "openalex": "W7163377912",
  "pdf_url": null,
  "pmcid": "PMC12236907",
  "pmid": "40630547",
  "published": "2026-06-03",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/44cq6attfaaqf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:54Z",
      "native_id": "W7163377912",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41586-026-10589-2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Microbial Natural Products and Biosynthesis",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "A natural depsipeptide antibiotic binds the E-site of the bacterial ribosome",
  "title_text": "A natural depsipeptide antibiotic binds the E-site of the bacterial ribosome",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T13:21:08Z",
  "url": "https://research.draconitic.com/paper/44cq6attfaaqf",
  "venue": "Nature",
  "versions": []
}