---
res:
  bibo_abstract:
  - The mammalian fatty acid synthase (FASN) enzyme is a dynamic multienzyme that
    belongs to the megasynthase family. In mammals, a single gene encodes six catalytically
    active domains and a flexibly tethered acyl carrier protein (ACP) domain that
    shuttles intermediates between active sites for fatty acid biosynthesis1. FASN
    is an essential enzyme in mammalian development through the role that fatty acids
    have in membrane formation, energy storage, cell signalling and protein modifications.
    Thus, FASN is a promising target for treatment of a large variety of diseases
    including cancer, metabolic dysfunction-associated fatty liver disease, and viral
    and parasite infections2,3. The multi-faceted mechanism of FASN and the dynamic
    nature of the protein, in particular of the ACP, have made it challenging to understand
    at the molecular level. Here we report cryo-electron microscopy structures of
    human FASN in a multitude of conformational states with NADPH and NADP+ plus acetoacetyl-CoA
    present, including structures with the ACP stalled at the dehydratase (DH) and
    enoyl-reductase (ER) domains. We show that FASN activity in vitro and de novo
    lipogenesis in cells is inhibited by mutations at the ACP–DH and ACP–ER interfaces.
    Together, these studies provide new molecular insights into the dynamic nature
    of FASN and the ACP shuttling mechanism, with implications for developing improved
    FASN-targeted therapeutics.@eng
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Kollin
      foaf_name: Schultz, Kollin
      foaf_surname: Schultz
  - foaf_Person:
      foaf_givenName: Pedro
      foaf_name: Costa-Pinheiro, Pedro
      foaf_surname: Costa-Pinheiro
  - foaf_Person:
      foaf_givenName: Lauren
      foaf_name: Gardner, Lauren
      foaf_surname: Gardner
      foaf_workInfoHomepage: http://www.librecat.org/personId=f9dedd98-6d15-11f0-88a5-a7b4143fdec5
    orcid: 0009-0000-5733-1546
  - foaf_Person:
      foaf_givenName: Laura V.
      foaf_name: Pinheiro, Laura V.
      foaf_surname: Pinheiro
  - foaf_Person:
      foaf_givenName: Julio
      foaf_name: Ramirez-Solis, Julio
      foaf_surname: Ramirez-Solis
  - foaf_Person:
      foaf_givenName: Sarah M.
      foaf_name: Gardner, Sarah M.
      foaf_surname: Gardner
  - foaf_Person:
      foaf_givenName: Kathryn E.
      foaf_name: Wellen, Kathryn E.
      foaf_surname: Wellen
  - foaf_Person:
      foaf_givenName: Ronen
      foaf_name: Marmorstein, Ronen
      foaf_surname: Marmorstein
  bibo_doi: 10.1038/s41586-025-08587-x
  bibo_issue: '8062'
  bibo_volume: 641
  dct_date: 2025^xs_gYear
  dct_isPartOf:
  - http://id.crossref.org/issn/0028-0836
  - http://id.crossref.org/issn/1476-4687
  dct_language: eng
  dct_publisher: Springer Nature@
  dct_title: Snapshots of acyl carrier protein shuttling in human fatty acid synthase@
  fabio_hasPubmedId: '39979457 '
...