{
  "abstract": "Nystatin, a polyene macrolide antifungal agent produced by Streptomyces noursei, exists as three major derivatives (nystatin A1, A3, polyfungin B) with distinct C-10 and C-35 modifications. Although the core catalytic functions of NysL and NysGtf have been established, the metabolic crosstalk between the C-10 hydroxylation and C-35 digitosylation branches, together with the in vivo substrate promiscuity of NysGtf in industrial S. noursei, remains poorly understood. In this study, we constructed gene-disruption, complementation and overexpression mutants of S. noursei 72-22-1 to characterize nysL and nysGtf. While NysL has previously been established as the C-10 hydroxylase, we characterized its role in the industrial derivative strain 72-22-1. nysL disruption abolished C-10 hydroxylation, eliminated nystatin A1/A3 and caused accumulation of 10-deoxynystatin and polyfungin B, while complementation and/or overexpression restored A1/A3 formation. nysGtf inactivation blocked C-35 glycosylation, raising nystatin A1 titer to 0.587 mg/mL and decreasing polyfungin B to 0.027 mg/mL. Its overexpression enhanced nystatin A3 production to 1.195 mg/mL. Our findings define the physiological roles of NysL and NysGtf in nystatin biosynthesis, identify polyfungin B as the key antifungal component, and provide a feasible strategy for metabolic engineering of S. noursei to generate high-activity nystatin derivatives.",
  "abstract_shown": true,
  "affiliations": [
    "School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China",
    "School of Functional Food and Wine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China",
    "School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China",
    "Beijing Global Biologicals Inc., 99 Yuexiu Road, Beijing 100192, China",
    "Care4living Oy, Itäinen Pitkäkatu 4, 20520 Turku, Finland",
    "Department of Life Technologies, University of Turku, Tykistökatu 6, 20520 Turku, Finland"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jibin Shi"
    },
    {
      "affs": [
        2
      ],
      "name": "Dexi Song"
    },
    {
      "affs": [
        0
      ],
      "name": "Junran Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xianpu Ni"
    },
    {
      "affs": [
        2
      ],
      "name": "Yitong Xu"
    },
    {
      "affs": [
        3
      ],
      "name": "Fuju Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Kristiina Ylihonko"
    },
    {
      "affs": [
        5
      ],
      "name": "Mikko Metsä-Ketelä"
    },
    {
      "affs": [
        1
      ],
      "name": "Ming Song",
      "orcid": "0000-0001-6996-8560"
    },
    {
      "affs": [
        1
      ],
      "name": "Weizhuo Xu",
      "orcid": "0000-0001-5641-4737"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fe0dcjpm7n9s6.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219572",
  "fulltext_url": null,
  "id": "fe0dcjpm7n9s6",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9572",
  "language": null,
  "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": [
    [
      "openalex",
      "2736|Microbial Natural Products and Biosynthesis"
    ]
  ],
  "openalex": "W7224005498",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/fe0dcjpm7n9s6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219572",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9572"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Microbial Natural Products and Biosynthesis",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Optimizing Nystatin Biosynthesis Through Targeted Manipulation of nysL and nysGtf in Streptomyces noursei",
  "title_text": "Optimizing Nystatin Biosynthesis Through Targeted Manipulation of nysL and nysGtf in Streptomyces noursei",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/fe0dcjpm7n9s6",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}