Hydrogenases utilize unusual organometallic metal centers to catalyze the reversible reduction of protons to H<sub>2</sub>. The catalytic H-cluster of the [FeFe]-hydrogenase is a carbon monoxide, cyanide, and dithiomethylamine-coordinated 2Fe subcluster bridged to a [4Fe-4S] cubane; reversible proton reduction occurs at the distal iron of the 2Fe subcluster. Biosynthesis of the H-cluster requires three specific maturase enzymes known as HydE, HydF, and HydG. HydE and HydG are both radical <i>S</i>-adenosylmethionine (SAM) enzymes that synthesize the nonprotein ligands of the H-cluster, while HydF is a GTPase that scaffolds 2Fe subcluster assembly prior to its transfer to hydrogenase. In a remarkable biochemical reaction, HydG cleaves tyrosine and decomposes the resulting dehydroglycine into carbon monoxide and cyanide ligands, with involvement of both a [4Fe-4S] cluster and a unique [5Fe-4S-Cys] complex. The role of HydE is less well defined although it is thought to use radical SAM chemistry to synthesize the bridging dithiolate ligand of the H-cluster. HydF is capable of binding multiple different iron-sulfur clusters, whose characteristics vary with experimental conditions and with the catalytic action of HydE and HydG. This lecture will focus on recent advances in elucidating the steps involved in the biosynthesis of the complex metal cluster at the [FeFe]-hydrogenase H-cluster.

Biosynthesis of the H-cluster of the [FeFe]-hydrogenase

255th National Meeting (2018)

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