Professor Seokmin Kim’s Team Develops World’s First Air-Stable Metalloenzyme Catalyst

The Catholic University of Korea Research Team Develops First-Ever Air-Stable Metalloenzyme Catalyst – Published in Angewandte Chemie

A research team led by Professor Seokmin Kim from the Department of Biotechnology at The Catholic University of Korea, in collaboration with Professor Yong-Hwan Kim (UNIST, Department of Energy and Chemical Engineering) and Professor Hyung-Ho Lee (Seoul National University, Department of Chemistry), has successfully developed the world’s first air-stable metalloenzyme catalyst.

This innovative catalyst maintains its activity even when exposed to air, overcoming a major limitation of conventional carbon monoxide dehydrogenase (CODH), which is highly sensitive to oxygen. The result marks a major step forward in biocatalytic processes for carbon neutrality.

Air-stable biocatalysts can dramatically reduce process costs in CO₂ and CO conversion, making them a core technology for realizing carbon neutrality. However, previous metalloenzymes like CODH have had limited industrial application due to extreme oxygen sensitivity.

To address this challenge, the research team engineered the substrate channel of Ni-Fe-S cluster-containing CODH to create a dual barrier system that selectively blocks oxygen from entering the enzyme's active site, while maintaining access for the substrate. Structural biology analysis (X-ray crystallography) confirmed that the CODH mutant maintained complete structural and functional integrity after more than 24 hours of exposure to air (20% oxygen), demonstrating unprecedented stability.

Furthermore, electrochemical analysis showed that the engineered CODH retained its catalytic activity for CO oxidation under aerobic conditions, overcoming the oxygen inhibition issue that has limited earlier versions (previous IC₉₀ ≈ 1 μM). Impressively, the newly developed variant showed 852-fold greater air stability, significantly surpassing a previous CODH mutant published as a cover article in Nature Catalysis (2022), which showed a 49-fold improvement.

This breakthrough was supported by Korea's Ministry of Science and ICT and the National Research Foundation under the Engineering Research Center (ERC) and the SMILE Project for Microplastics Response. The findings were published on June 4 as a back-cover article in Angewandte Chemie International Edition (Impact Factor: 16.1, JCR top 5.8%), and were selected as a Hot Paper, recognizing it as one of the top 10% most noteworthy studies in the journal.

Professor Seokmin Kim commented:

“This research not only enables breakthroughs in CODH but also holds great promise for stabilizing other oxygen-sensitive metalloenzymes like hydrogenases and CO₂-reducing enzymes. We expect it will lead to disruptive innovations in biological hydrogen production and greenhouse gas reduction technologies.”