{
  "abstract": "Combining biosynthetic enzymes from distinct ribosomally synthesized and post-translationally modified peptide (RiPP) families offers a route to hybrid RiPPs but poses challenges in coordinating noncognate enzymatic transformations. Here, leveraging the temporal control enabled by in vitro biosynthesis, we first explored stage-defined integration of a cyanobactin prenyltransferase (PTase) into thiopeptide biosynthesis, a highly coordinated multienzyme pathway involving interdependent transformations of a single precursor peptide. Whereas early- and intermediate-stage prenylation interfered with thiopeptide maturation, late-stage prenylation of fully matured thiopeptides proceeded efficiently, enabling the production of diverse prenylated thiopeptides. We then extended this late-stage strategy to structurally distinct RiPPs, nonribosomal peptides, and artificial cyclic peptides using multiple cyanobactin PTases. Stage-controlled integration of non-cognate tailoring enzymes thus provides access to hybrid peptidic natural products.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, Graduate School of Science",
    "Kyoto University",
    "University of Tokyo",
    "Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Vladimir-Prelog-Weg 4, Zurich, Switzerland, 8093",
    "Toyota Riken Rising Fellow"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Sota Uchida"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Taro Shiraishi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Marin Yokomine"
    },
    {
      "affs": [
        3
      ],
      "name": "Julien Alessandro König"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhong Hui Lim"
    },
    {
      "affs": [
        3
      ],
      "name": "Dora Racunica"
    },
    {
      "affs": [
        3
      ],
      "name": "Anna L. Vagstad"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Hiroaki Suga"
    },
    {
      "affs": [
        3
      ],
      "name": "Jörn Piel"
    },
    {
      "affs": [
        0,
        1,
        2,
        4
      ],
      "name": "Yuki Goto",
      "orcid": "0000-0003-4317-0790"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/423txp9018em5.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009020/v1",
  "fulltext_url": null,
  "id": "423txp9018em5",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009020/v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2736|Microbial Natural Products and Biosynthesis"
    ]
  ],
  "openalex": "W7213535346",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009020/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/423txp9018em5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.26434/chemrxiv.15009020",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009020/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Microbial Natural Products and Biosynthesis",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Stage-Defined Prenyltransferase Integration for Hybrid RiPP Biosynthesis",
  "title_text": "Stage-Defined Prenyltransferase Integration for Hybrid RiPP Biosynthesis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/423txp9018em5",
  "venue": "ChemRxiv",
  "versions": []
}