{
  "abstract": "Lipoic acid (1,2-dithiolane-3-pentanoic acid or 6,8-thioctic acid) is a sulfur-containing cofactor essential for central metabolism, where it functions in oxidative decarboxylation reactions catalyzed by the 2-oxoacid dehydrogenase complexes and glycine degradation catalyzed by the glycine cleavage system. Beyond its canonical metabolic roles, the redox-active disulfide/dithiol pair of lipoic acid has attracted considerable interest because of its proposed therapeutic relevance in ailments associated with oxidative stress and inflammation, such as Alzheimer's and Parkinson's disease. Despite the broad biological importance of this cofactor, the molecular details of its biosynthesis remained elusive for many years because of the unusual chemistry required for sulfur insertion into unactivated carbon centers. Recent advances have subsequently expanded the understanding of this pathway, particularly through mechanistic and structural studies of lipoyl synthase, a radical S-adenosylmethionine enzyme that catalyzes sulfur incorporation during cofactor assembly. This perspective highlights current insights into lipoic acid biosynthesis and lipoyl synthase, with an emphasis on emerging mechanistic paradigms, lipoyl synthase auxiliary cluster function and regeneration, and the broader biochemical context of radical-mediated sulfur insertion.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.",
    "Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, United States.",
    "Department of Biochemistry & Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.",
    "Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.",
    "Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Olga E Esakova"
    },
    {
      "affs": [
        0
      ],
      "name": "Caitlin D Palmer"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Douglas M Warui"
    },
    {
      "affs": [
        2
      ],
      "name": "Erin L McCarthy"
    },
    {
      "affs": [
        3,
        0,
        2,
        4,
        1
      ],
      "name": "Squire J Booker",
      "orcid": "0000-0002-7211-5937"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/29mx36wrggjp1.bib",
  "cited_by": 0,
  "doi": "10.1021/acsbiomedchemau.6c00104",
  "fulltext_url": "https://europepmc.org/articles/PMC13692748",
  "id": "29mx36wrggjp1",
  "issns": [
    "2694-2437"
  ],
  "landing_url": "https://europepmc.org/article/MED/42921321",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1303|Biochemical Acid Research Studies"
    ]
  ],
  "openalex": "W7171389137",
  "pdf_url": "https://europepmc.org/articles/PMC13692748?pdf=render",
  "pmcid": "PMC13692748",
  "pmid": "42921321",
  "published": "2026-07-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/29mx36wrggjp1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42921321",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921321"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1303|Biochemical Acid Research Studies",
      "subfield": "general"
    }
  ],
  "title": "Lipoyl Synthase in Focus: Radical SAM Chemistry and the Biosynthesis of Lipoic Acid.",
  "title_text": "Lipoyl Synthase in Focus: Radical SAM Chemistry and the Biosynthesis of Lipoic Acid.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/29mx36wrggjp1",
  "venue": "ACS bio & med chem Au",
  "versions": []
}