A recent study has shed light on the exceptional oxygen resistance of the [FeFe]-hydrogenase CbA5H from Clostridium beijerinckii, a bacterium known for surviving in oxygen-rich environments. Unlike most hydrogen-producing enzymes that are vulnerable to oxygen, CbA5H has intrigued researchers due to its ability to function effectively in the presence of oxygen. The collaborative effort between researchers at Ruhr University Bochum and Osaka University has led to significant discoveries regarding the molecular mechanisms that enable CbA5H to thrive in oxygenated conditions. By utilizing cryoEM, the team obtained a complete structure of CbA5H under anoxic conditions, unveiling crucial insights into its O2 protection strategy and hydrogen production process. The study's findings highlighted the role of a sulfur-containing group that shields the active center of CbA5H, thus safeguarding it from oxygen damage. Moreover, the research revealed the significance of Zn2+-mediated dimerization in enhancing the stability of CbA5H, where the homodimeric form proved to be more robust in the absence of Zn2+. These structural determinants not only elucidate the working mechanisms of CbA5H but also offer a potential path for developing novel oxygen-resistant [FeFe]-hydrogenases for efficient hydrogen production. Overall, the study contributes valuable knowledge to the field of biocatalysts by providing key insights into the structural composition, oxygen resistance, and stability mechanisms of CbA5H. The research paves the way for future advancements in optimizing hydrogen-producing enzymes, aiming to facilitate sustainable hydrogen production for various industrial applications.