{
  "abstract": "FK228 (romidepsin) is a potent HDAC inhibitor; however, its clinical application is severely constrained by low natural yields and the genetic intractability of its native producer. Here, we leveraged the established Burkholderia chassis KOGC1 to develop a high-performance platform for FK228 production. Through systematic fermentation optimization, we addressed major production constraints including potential end-product toxicity and precursor supply. Specifically, the integration of XAD-16 resin adsorption together with the combined feeding of key amino acids (cysteine, valine, and threonine) elevated the titer to 743.5 mg/L. Subsequent refactoring of the biosynthetic gene cluster and promoter engineering further increased the titer to 1109.4 mg/L. Furthermore, the engineered strain exhibited remarkable genetic stability over five generations without antibiotic selection, which may help address a key barrier to future scale-up. Overall, this study establishes a highly productive laboratory-scale FK228 biosynthetic platform, providing a foundation for future process development of this important therapeutic agent.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Microbial Technology, Shandong University",
    "NHC Key Lab of Reproduction Regulation, Shanghai Engineering Research Center of Reproductive Health Drugs and Devices, Shanghai Institute for Biomedical and Pharmaceutical Technologies"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maoqin Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuexin Jia"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunling Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Junchi Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Youming Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jun Fu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruijuan Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/46nty98qvfv5a.bib",
  "cited_by": 0,
  "doi": "10.3389/fmicb.2026.1933794",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13716795/?tool=EBI",
  "id": "46nty98qvfv5a",
  "issns": [
    "1664-302X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fmicb.2026.1933794/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2736|Microbial Natural Products and Biosynthesis"
    ]
  ],
  "openalex": "W7222251150",
  "pdf_url": "https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2026.1933794/pdf",
  "pmcid": "PMC13716795",
  "pmid": "42959159",
  "published": "2026-10-15",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/46nty98qvfv5a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:12Z",
      "native_id": "10.3389/fmicb.2026.1933794",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fmicb.2026.1933794/full"
    },
    {
      "first_seen": "2026-10-31T00:20:37Z",
      "native_id": "PMC:PMC13716795",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13716795"
    },
    {
      "first_seen": "2026-11-01T00:20:52Z",
      "native_id": "MED:42959159",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42959159"
    },
    {
      "first_seen": "2026-11-01T12:24:00Z",
      "native_id": "PMC13716795",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fmicb.2026.1933794"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Microbial Natural Products and Biosynthesis",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Engineering the FK228 biosynthetic gene clusters for high-yield production",
  "title_text": "Engineering the FK228 biosynthetic gene clusters for high-yield production",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:14Z",
  "url": "https://research.draconitic.com/paper/46nty98qvfv5a",
  "venue": "Frontiers in Microbiology",
  "versions": []
}