Emerging [FeFe]-hydrogenases: oxygen protection mechanisms and biotechnological potential

Abstract

The remarkable diversity of enzymes involved in H 2 metabolism provides unique insights into the molecular strategies evolved by nature to overcome challenges in redox chemistry. Among hydrogenases, [FeFe]-hydrogenases contain the H-cluster, a unique metallocofactor that enables rapid and reversible H 2 conversion at minimal overpotential, making them attractive biocatalysts for future hydrogen technologies. This review highlights how the discovery and characterisation of novel [FeFe]-hydrogenases are reshaping our understanding of H-cluster chemistry, enzyme architecture, and biological function. Recent studies have revealed unexpected diversity of structural and functional features, providing fresh perspectives on long-standing questions surrounding enzyme mechanisms and stability. In particular, O 2 -protected [FeFe]-hydrogenases are revealing new mechanisms of aerobic protection while presenting clear advantages for biotechnological implementation, by removing the need for stringent anaerobic handling and facilitating large-scale production. Together, these discoveries elucidate fundamental principles of biological redox catalysis and expand opportunities for sustainable hydrogen biotechnologies.

The authors' abstract, as published at the source. Current Opinion in Chemical Biology, 2026 · DOI ↗