{
  "abstract": "2 ABSTRACT: Tropolone-containing natural products display diverse biological activities, yet characterized fungal tropolone hybrids are dominated by sesquiterpene-derived systems, leaving polyketide-tropolone hybridization largely unexplored. Here, genome mining guided by conserved tropolone biosynthetic enzymes and an unusual dual-polyketide synthase architecture led to the discovery of fusariolones A–E and semifusariolone A from Fusarium sp. WA57, defining a distinct family of fungal polyketide-tropolone hybrids. Heterologous pathway reconstitution supported fusABCDEF as the minimal gene set for scaffold assembly and revealed a biosynthetic logic in which a canonical tropolone pathway converges with a highly reducing polyketide synthase. The resulting linear pentaene hydrocarbon represents, to the best of our knowledge, the first such intermediate identified in fungal natural product biosynthesis and supports a proposed FusF-mediated dehydration/hetero-Diels-Alder cascade in scaffold construction. Fusariolone A displayed low-nanomolar antiproliferative activity with pronounced selectivity toward K562 and HT-29 cells. In HT-29 cells, it suppressed DNA synthesis, altered cell cycle progression, and increased apoptosis, while also reducing xenograftassociated fluorescence in zebrafish. Together, these findings establish a distinct biosynthetic strategy for polyketide-tropolone hybrid assembly and expand the chemical and functional space of fungal tropolone natural products.",
  "abstract_shown": true,
  "affiliations": [
    "Guangzhou Key Laboratory of Formula-Pattern Research Centre School of Traditional Chinese Medicine",
    "Jinan University Guangzhou"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Changzheng Wu"
    },
    {
      "name": "Yanfu Wang"
    },
    {
      "name": "Daixi Liu"
    },
    {
      "name": "Leyuan Yu"
    },
    {
      "name": "Zhanghao Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lijuan Deng"
    },
    {
      "name": "Runping Fang"
    },
    {
      "name": "Jianhua Ju"
    },
    {
      "name": "Haiyan Tian"
    },
    {
      "name": "Zhuo Shang",
      "orcid": "0000-0002-5755-2629"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/81hvtfq5kymqv.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010572/v1",
  "fulltext_url": null,
  "id": "81hvtfq5kymqv",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010572/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": "W7222425232",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010572/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/81hvtfq5kymqv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10.26434/chemrxiv.15010572",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010572/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Microbial Natural Products and Biosynthesis",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Genome Mining-Guided Discovery of Polyketide-Tropolone Hybrids Reveals Their Biosynthetic Logic and Antitumor Activity",
  "title_text": "Genome Mining-Guided Discovery of Polyketide-Tropolone Hybrids Reveals Their Biosynthetic Logic and Antitumor Activity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:24Z",
  "url": "https://research.draconitic.com/paper/81hvtfq5kymqv",
  "venue": "ChemRxiv",
  "versions": []
}