{
  "abstract": "Sulfonolipids are bacterial sphingolipid-like lipids featuring a sulfonated long-chain base derived from cysteate. Although several cysteate-utilizing enzymes have been implicated in sulfonolipid biosynthesis, their phylogenetic relationships and the structural basis of cysteate utilization remain poorly understood. Here, we combined phylogenetic analysis, biochemical characterization, X-ray crystallography, and mutagenesis to investigate cysteate fatty acyltransferase (CFAT) homologues involved in bacterial sulfonolipid biosynthesis. Phylogenetic analysis revealed that previously characterized cysteate-utilizing enzymes form a distinct branch within the broader serine palmitoyltransferase (SPT)-related pyridoxal 5'-phosphate (PLP)-dependent enzyme superfamily. Biochemical assay on six representatives confirmed a conserved cysteate-dependent long-chain-base synthase activity and a strong preference for cysteate over serine, glycine, and alanine. To elucidate this specificity, we solved crystal structures of a representative CFAT from Capnocytophaga ochracea in both PLP-bound and PLP-cysteate-bound states, capturing a PLP-cysteate external aldimine intermediate. This structure reveals a composite active-site pocket formed across the dimer interface, where the conserved PLP-dependent catalytic scaffold is retained but the substrate-binding pocket is significantly remodeled compared to canonical SPTs. Structure-guided mutagenesis identified key residues important for cysteate-dependent catalysis but failed to generate serine activity. Together, these findings establish CFAT homologues as a functionally coherent family of cysteate-utilizing enzymes and provide critical molecular insights into bacterial sulfonolipid biosynthesis.",
  "abstract_shown": true,
  "affiliations": [
    "International Cancer Center, School of Pharmacy, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Shenzhen University Medical School, Shenzhen 518055, China.",
    "Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China.",
    "Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.",
    "State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.",
    "School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.",
    "Shenzhen Medical Academy of Research and Translation, Shenzhen 518107, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Cuiping Pang"
    },
    {
      "affs": [
        1
      ],
      "name": "Meihan Liu"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yang Gu",
      "orcid": "0009-0008-3508-1337"
    },
    {
      "affs": [
        2,
        4
      ],
      "name": "Jiahai Zhou"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Xiaoyu Tang",
      "orcid": "0000-0002-7855-5984"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f8ctz4atq1m7m.bib",
  "cited_by": 0,
  "doi": "10.1021/acsbiomedchemau.6c00154",
  "fulltext_url": "https://europepmc.org/articles/PMC13692747",
  "id": "f8ctz4atq1m7m",
  "issns": [
    "2694-2437"
  ],
  "landing_url": "https://europepmc.org/article/MED/42921287",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1303|Lipid metabolism and biosynthesis"
    ]
  ],
  "openalex": "W7204056203",
  "pdf_url": "https://europepmc.org/articles/PMC13692747?pdf=render",
  "pmcid": "PMC13692747",
  "pmid": "42921287",
  "published": "2026-08-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f8ctz4atq1m7m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42921287",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921287"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1303|Lipid metabolism and biosynthesis",
      "subfield": "enzymology-metabolism"
    }
  ],
  "title": "Structural and Functional Characterization of Cysteate Fatty Acyltransferases Involved in Bacterial Sulfonolipid Biosynthesis.",
  "title_text": "Structural and Functional Characterization of Cysteate Fatty Acyltransferases Involved in Bacterial Sulfonolipid Biosynthesis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/f8ctz4atq1m7m",
  "venue": "ACS bio & med chem Au",
  "versions": []
}