Microbial hydrogen metabolism
Like formate, hydrogen represents an important energy source for a multitude of microorganisms on this planet. Hydrogen produced by many fermenting microorganisms is also a means of removing redox equivalents from the cell. Hydrogen metabolism has also been a key driver in the evolution of life on earth. As such, the study of hydrogenases, the enzymes that reversibly activate hydrogen, is important not only in understanding the energetics of microbial growth but also with regard to how they have rightly garnered biotechnological interest due to their potential use in alternative energy storage. Of these enzymes, the class of [NiFe]-hydrogenases is the most abundant and most ancient. [NiFe]-hydrogenases catalyze both oxidation of hydrogen, to provide reducing equivalents, and reduction of protons to generate hydrogen. We have two main research interests in [NiFe]-hydrogenase:
1. The biosynthesis of the [NiFe]-hydrogenases, particularly that of their active site, is of considerable interest because it represents a lucid example of coordinated metallo-cofactor assembly. The Fe of the [NiFe]-cofactor is decorated with three diatomic ligands, one carbonyl and two cyanyl moieties. These ligands are so far unprecedented in biology and their function is to modulate the redox properties of the cofactor facilitating hydrogen cleavage or formation. Six Hyp proteins are highly conserved and required in all organisms that synthesize [NiFe]-hydrogenases. Our group is interested in how this [NiFe]-cofactor is assembled and inserted into the apo-hydrogenase catalytic subunit.
2. We are also interested in understanding how the bioenergetics of [NiFe]-hydrogenases influences the physiology of bacteria. We work with the deeply branching and obligately organohalide-respiring Dehalococcoides genus and with E. coli, a member of the enterobacteria that both produces and consumes hydrogen. Dehalococcoides spp. use hydrogen as an energy source and what is intriguing is that their respiratory chain lacks quinones. Consequently, electron transport between respiratory enzyme complexes requires direct protein-protein interaction. Moreover, the respective active site of both components of the simple respiratory chain in these bacteria is on the outside of the cytoplasmic membrane, implying that energy conservation likely involves proton-pumping mechanisms to allow generation of a chemiosmotic proton gradient. The hydrogenase of these bacteria is related to the [NiFe]-hydrogenase 2 of E. coli and lacks a quinone-binding site. In terms of evolution, these related enzymes potentially represents an prototypical form of [NiFe]-hydrogenase. We are therefore interested in electron and proton transport catalyzed by these enzymes and how they enable energy conservation.
Hydrogenase 1 active site
Pinske C, Sawers RG: The importance of iron in the biosynthesis and assembly of [NiFe]-hydrogenases. Biomol Concepts 2014, 5:55–70.