Student Posters 51st Lorne Proteins Conference 2026

Discovery of Oxygen-Stable [FeFe]-Hydrogenases in Human Gut Bacteroides (#138)

Warunika Karunasiri 1 2 , Marion Jespersen 1 , Thomas D. Watts 1 , Samuel C. Forster 2 , Chris Greening 1
  1. Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
  2. Centre for Innate Immunity and Infectious Disease, Hudson Institute of Medical Research, Clayton, Victoria, Australia

The human gastrointestinal tract (gut) harbours trillions of bacteria, the majority of which are strictly anaerobic and rely on fermentation. Hydrogen (H2) is a major gaseous product of fermentation, serving to dispose of excess reductants. Although H2 dysbiosis is linked to gut and systemic disorders, H2 metabolism within the gut remains largely uncharacterized. The production and consumption of H2 are catalysed by hydrogenase enzymes. A recent study found that the previously unrecognized group B [FeFe]-hydrogenases are the most widespread and highly expressed gut hydrogenases in humans, primarily found in Bacteroides. While [FeFe]-hydrogenases are highly efficient enzymes with significant biotechnological potential, their oxygen sensitivity limits their exploitation for practical applications. This includes group A [FeFe]-hydrogenases, which show the greatest predicted structural similarity to group B; however, group B hydrogenases have an additional flexible ferredoxin domain absent in group A. We tested a panel of Bacteroides species; B. thetaiotaomicron, B. fragilis and B. plebeius for their oxygen stability and H2 production. Notably, the TSCCCP motif, recently identified as a key factor for oxygen stability in the group B [FeFe]-hydrogenase of Thermosediminibacter oceani, is absent in all investigated group B [FeFe]-hydrogenases from Bacteroides. However, these enzymes remained oxygen-stable throughout our native purification process. Among the three species tested, B. plebeius showed the highest hydrogenase activity, while B. thetaiotaomicron retained an activity of 0.1 µmol/min/mg after native purification, even following three weeks of exposure to air. Hence, in this study, we aim to provide the first structural and biochemical insights into Bacteroides group B [FeFe]-hydrogenases to enhance our understanding of microbial H2 metabolism in the human gut and to improve prospects for future applications such as green H2 generation. 

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