Filamentation of the bacterial bi-functional alcohol/aldehyde dehydrogenase AdhE is essential for substrate channeling and enzymatic regulation
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Abstract
Abstract Acetaldehyde – alcohol dehydrogenase (AdhE) enzymes are a key metabolic enzyme in bacterial physiology and pathogenicity. They convert acetyl-CoA to ethanol via an acetaldehyde intermediate during ethanol fermentation in anaerobic environment. This two-step reaction is associated to NAD + regeneration, essential for glycolysis. The bifunctional AdhE enzyme is conserved in all bacterial kingdoms but also in more phylogenetically distant microorganisms such as green microalgae. In synthetic biology and biotechnology, because of its central role in bacterial alcoholic fermentation, AdhE raised a lot of attention as a key enzyme to produce ethanol from bacterial cultures. AdhE is commonly found as an oligomeric form called spirosomes. While these helical macromolecular assemblies are conserved, their function remains elusive. We used cryo-electron microscopy to obtain structures of Escherichia coli spirosomes in different conformational states. We confirm that spirosomes contain active AdhE monomers and show that AdhE filamentation is essential for its activity in vitro and function in vivo . The detailed analysis of these structures provides insight showing that AdhE filamentation is essential for substrate channeling within the filament and for the regulation of enzyme activity. These new data will help to design molecules or mutations that control AdhE activity to fight bacterial pathogens or to optimize ethanol production in biotechnology.
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Bacteria possess a bifunctional enzyme, acetaldehyde-alcohol dehydrogenase (AdhE), which exhibits both aldehyde dehydrogenase (AlDH) and alcohol dehydrogenase (ADH) activities; under anaerobic conditions, AdhE can convert acetyl-CoA to ethanol; this process generates energy and maintains the intracellular NAD+/NADH balance by oxidizing NADH and regenerating NAD+, which is essential for sustaining
“Simultaneously, bacteria possess a bifunctional enzyme, acetaldehyde-alcohol dehydrogenase (AdhE), which exhibits both aldehyde dehydrogenase (AlDH) and alcohol dehydrogenase (ADH) activities. Under anaerobic conditions, AdhE can convert acetyl-CoA to ethanol. This process not only generates energy but also maintains the intracellular NAD+/NADH balance by oxidizing NADH and regenerating NAD+,”
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- Authors
- Pony, P., Rapisarda, C., Terradot, L., Marza, E., & Fronzes, R.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Marza, Esther
- Fronzes, Rémi
- Venue
- Nature Communications
- Published
- 2020-03-18
- Volume
- 11
- Issue
- 1
- Pages
- 1426-1426
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7080775
- OpenAlex
- W3012001250
- Cited by
- 82
- References
- 35
- Citations by year
- 2026: 17 · 2025: 18 · 2024: 18 · 2023: 10 · 2022: 9 · 2021: 7 · 2020: 3
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Centre National de la Recherche Scientifique
- Université de Bordeaux
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- AdhE, filamentation, substrate channeling, enzyme oligomerization, alcoholic fermentation, NAD+ regeneration, enzyme regulation, Escherichia coli, cryo-electron microscopy, enzyme conformational states
- MeSH terms
- Alcohol Dehydrogenase, Ethanol, Aldehyde Oxidoreductases, Aldehydes, Escherichia coli, Models, Molecular, Escherichia coli Proteins
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