Engineering the Electron Relay in [FeFe]-Hydrogenase Enhances Electrocatalytic H<sub>2</sub> Evolution

Journal article

H2 is an ideal energy vector, but catalysts for its clean production from water are inefficient or expensive. [FeFe]-hydrogenases are the most active H2-converting catalysts in nature, using a unique organometallic active site finely tuned by the protein matrix. M3 type [FeFe]-hydrogenases from Clostridium pasteurianum and Clostridium acetobutylicum are exceptionally active for H2 production, and less O2 sensitive than most other types of [FeFe]-hydrogenases, making them attractive targets for biotechnology. However, they are more challenging to work with because of their large size and the number of iron-sulfur clusters. Here, the [FeFe]-hydrogenase from C. acetobutylicum was systematically engineered to truncate each iron-sulfur-containing region of the F-domain, yielding smaller and easier-to-produce catalytic systems. Detailed characterization revealed that these variants retain high electrocatalytic performance and other essential properties of the natural enzyme.

Authors: Lai, TP; Myers, WK; Carr, SB; Ramirez, MA; Vincent, KA

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Chemical Society
• Journal: ACS Catalysis
• Volume: 15
• Issue: 22
• Pages: 19216-19226
• Publication date: 2025-11-05
• Acceptance date: 2025-10-21
• DOI: 10.1021/acscatal.5c03665
• EISSN: 2155-5435
• ISSN: 2155-5435
• Pmid: 41307037
• Language: English
• Keywords: Electrocatalysis; Catalytic Bias; H2-Conversion; Inhibitor Sensitivity; Metalloenzymes; Truncations