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TitleStructural characterization and dynamics of AdhE ultrastructures from show a containment strategy for toxic intermediates.
Journal, issue, pagesElife, Vol. 13, Year 2025
Publish dateJun 27, 2025
AuthorsSamantha J Ziegler / Brandon C Knott / Josephine N Gruber / Neal N Hengge / Qi Xu / Daniel G Olson / Eduardo E Romero / Lydia-Marie Joubert / Yannick J Bomble /
PubMed Abstract, a cellulolytic thermophilic anaerobe, is considered by many to be a prime candidate for the realization of consolidated bioprocessing (CBP) and is known as an industry standard for biofuel ..., a cellulolytic thermophilic anaerobe, is considered by many to be a prime candidate for the realization of consolidated bioprocessing (CBP) and is known as an industry standard for biofuel production. is among the best biomass degraders identified to date in nature and produces ethanol as one of its main products. Many studies have helped increase ethanol titers in this microbe; however, ethanol production using is still not economically viable. Therefore, a better understanding of its ethanol synthesis pathway is required. The main pathway for ethanol production in involves the bifunctional aldehyde-alcohol dehydrogenase (AdhE). To better understand the function of the AdhE, we used cryo-electron microscopy (cryo-EM) to obtain a 3.28 Å structure of the AdhE complex. This high-resolution structure, in combination with molecular dynamics simulations, provides insight into the substrate channeling of the toxic intermediate acetaldehyde, indicates the potential role of AdhE to regulate activity and cofactor pools, and establishes a basis for future engineering studies. The containment strategy found in this enzyme offers a template that could be replicated in other systems where toxic intermediates need to be sequestered to increase the production of valuable biochemicals.
External linksElife / PubMed:40577193 / PubMed Central
MethodsEM (single particle)
Resolution3.28 Å
Structure data

42284

8uhw

EMDB-42284, PDB-8uhw:
The structure of the Clostridium thermocellum AdhE spirosome
Method: EM (single particle) / Resolution: 3.28 Å

Chemicals

ChemComp-FE:
Unknown entry

Source
  • acetivibrio thermocellus dsm 1313 (bacteria)
KeywordsOXIDOREDUCTASE / Aldehyde-alcohol dehydrogenase / Complex / Spirosome

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