Microorganism-derived enzymes exhibit the potential to produce hydrogen (H2) for biobased H2 technologies. However, efficiency in hydrogen production faces challenges, including the inhibitory effects of naturally occurring formaldehyde on the highly efficient [FeFe] hydrogenase. Researchers from Ruhr University Bochum's Photobiotechnology workgroup in Germany have successfully unraveled and mitigated this limiting mechanism, presenting their findings in the Journal of the American Chemical Society on November 20, 2023.
Formaldehyde, commonly recognized as a preservative, also serves as a natural metabolite in living cells. A dozen years ago, scientists from the University of Oxford and Ruhr University Bochum revealed that this ubiquitous molecule hampers a specific class of biocatalysts—the highly efficient hydrogen-generating hydrogenases of the [FeFe] type.
“This was an intriguing discovery, as formaldehyde could impede both the natural H2 metabolism of microorganisms and isolated hydrogenases in biotechnological applications,” explains Dr. Jifu Duan, the study's first author.
Building on theoretical studies that speculated on formaldehyde's impact on [FeFe]-hydrogenases, a research team led by Duan and Professor Eckhard Hofmann at Ruhr University has now experimentally elucidated the molecular mechanism. Using structures of formaldehyde-treated [FeFe]-hydrogenases obtained through protein crystallography, they demonstrated that formaldehyde reacts with the biocatalysts' active center—an inorganic protein region where protons and electrons are converted into H2.
Furthermore, formaldehyde interacts with another crucial protein segment essential for proton transport to the active center via a sulfur-containing chemical group. By replacing this segment with an alternative, formaldehyde's inhibitory effect was significantly diminished.
“In future biotechnological applications of [FeFe]-hydrogenases, the presence of formaldehyde may be inevitable, making our modified formaldehyde-resistant biocatalysts applicable,” notes Duan. “We also believe that our findings can be applied to other biocatalysts.” This could prove significant for bio-based industrial processes and enhance our understanding of metabolic pathways in living organisms.