Carbon-monoxide-driven bioethanol production operates through a tungsten-dependent catalyst
Abstract
Microbial alcohol production from waste gases is a game changer for sustainable carbon cycling and remediation. While the biotechnological process using Clostridium autoethanogenum to transform syngas (H 2 , CO 2 and CO) is blooming, scientific debates remain on the ethanol biosynthesis pathway. Here, we experimentally validated that ethanol production is initiated through a tungsten-dependent aldehyde:ferredoxin oxidoreductase (AFOR), which reduces acetate to acetaldehyde. The reaction, thermodynamically unfavorable under standard conditions, has been considered by many as unsuitable in vivo but is rather approved by metabolic modeling. To answer this riddle, we demonstrated that the thermodynamic coupling of CO oxidation and ethanol synthesis allows acetate reduction. The experiments, performed with native CO dehydrogenase and AFOR, highlighted the key role of ferredoxin in stimulating the activity of both metalloenzymes and electron shuttling. The crystal structure of holo AFOR, refined to 1.59-Å resolution, and its biochemical characterization provide new insights into the cofactor chemistry and the specificities of this enzyme, fundamental to sustainable biofuel production.
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BibTeX
@article{lemaire2026carbonmonoxidedriven,
title = {{Carbon-monoxide-driven bioethanol production operates through a tungsten-dependent catalyst}},
author = {Olivier Lemaire and Mélissa Belhamri and Anna Shevchenko and Tristan Wagner},
journal = {Nature Chemical Biology},
year = {2026},
month = sep,
doi = {10.1038/s41589-025-02055-3},
url = {https://hal.science/hal-05740980v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Carbon-monoxide-driven bioethanol production operates through a tungsten-dependent catalyst
AU - Olivier Lemaire
AU - Mélissa Belhamri
AU - Anna Shevchenko
AU - Tristan Wagner
PY - 2026
DA - 2026/09/07
JO - Nature Chemical Biology
DO - 10.1038/s41589-025-02055-3
UR - https://hal.science/hal-05740980v1
AB - Microbial alcohol production from waste gases is a game changer for sustainable carbon cycling and remediation. While the biotechnological process using Clostridium autoethanogenum to transform syngas (H 2 , CO 2 and CO) is blooming, scientific debates remain on the ethanol biosynthesis pathway. Here, we experimentally validated that ethanol production is initiated through a tungsten-dependent aldehyde:ferredoxin oxidoreductase (AFOR), which reduces acetate to acetaldehyde. The reaction, thermodynamically unfavorable under standard conditions, has been considered by many as unsuitable in vivo but is rather approved by metabolic modeling. To answer this riddle, we demonstrated that the thermodynamic coupling of CO oxidation and ethanol synthesis allows acetate reduction. The experiments, performed with native CO dehydrogenase and AFOR, highlighted the key role of ferredoxin in stimulating the activity of both metalloenzymes and electron shuttling. The crystal structure of holo AFOR, refined to 1.59-Å resolution, and its biochemical characterization provide new insights into the cofactor chemistry and the specificities of this enzyme, fundamental to sustainable biofuel production.
SN - 1552-4450
SN - 1552-4469
ER -