Metal cofactor-level chassis engineering enables aerobic expression of tungsten formate dehydrogenases in Escherichia coli
- 1School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, South Korea
- 2Department of Chemical & Biological Engineering, Korea University, Seoul, South Korea
- 3Graduate School of Carbon Neutrality, Ulsan National Institute of Science and Technology, Ulsan, South Korea
Abstract
Tungsten-dependent formate dehydrogenases are among the most active biological catalysts for carbon dioxide reduction, but their production is limited by complex metal cofactor requirements and poor compatibility with standard expression hosts. Here, we address this limitation by engineering an Escherichia coli chassis through reconstruction of tungsten cofactor biosynthesis, installation of a high-affinity tungstate transporter, and reinforcement of iron–sulfur cluster biogenesis. The resulting chassis produces the formate dehydrogenase from Methylorubrum extorquens with native-level specific activity, near-stoichiometric tungsten incorporation, and high volumetric activity, while substantially enhancing whole-cell CO-driven CO₂-to-formate conversion compared with the native-host system. The engineered host demonstrates broad applicability by supporting maturation of tungsten-dependent formate dehydrogenases from Cupriavidus necator, Lutibaculum baratangense, Thermococcus onnurineus, and Thermoanaerobacter kivui. In this work, we show that engineering host metal cofactor metabolism provides a strategy for aerobic production of active tungsten-dependent formate dehydrogenases, expanding access to this enzyme family for biological and biotechnological applications.
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BibTeX
@article{phan2026metal,
title = {{Metal cofactor-level chassis engineering enables aerobic expression of tungsten formate dehydrogenases in Escherichia coli}},
author = {Uyen Thu Phan and Jun-Min Lee and Toan Minh Vo and Min-Kyu Oh and Yong Hwan Kim},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-78159-8},
url = {https://doi.org/10.1038/s41467-026-78159-8},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Metal cofactor-level chassis engineering enables aerobic expression of tungsten formate dehydrogenases in Escherichia coli
AU - Uyen Thu Phan
AU - Jun-Min Lee
AU - Toan Minh Vo
AU - Min-Kyu Oh
AU - Yong Hwan Kim
PY - 2026
DA - 2026/09/28
JO - Nature Communications
DO - 10.1038/s41467-026-78159-8
UR - https://doi.org/10.1038/s41467-026-78159-8
AB - Tungsten-dependent formate dehydrogenases are among the most active biological catalysts for carbon dioxide reduction, but their production is limited by complex metal cofactor requirements and poor compatibility with standard expression hosts. Here, we address this limitation by engineering an Escherichia coli chassis through reconstruction of tungsten cofactor biosynthesis, installation of a high-affinity tungstate transporter, and reinforcement of iron–sulfur cluster biogenesis. The resulting chassis produces the formate dehydrogenase from Methylorubrum extorquens with native-level specific activity, near-stoichiometric tungsten incorporation, and high volumetric activity, while substantially enhancing whole-cell CO-driven CO₂-to-formate conversion compared with the native-host system. The engineered host demonstrates broad applicability by supporting maturation of tungsten-dependent formate dehydrogenases from Cupriavidus necator, Lutibaculum baratangense, Thermococcus onnurineus, and Thermoanaerobacter kivui. In this work, we show that engineering host metal cofactor metabolism provides a strategy for aerobic production of active tungsten-dependent formate dehydrogenases, expanding access to this enzyme family for biological and biotechnological applications.
SN - 2041-1723
ER -