A radical solution for the biosynthesis of the H‐cluster of hydrogenase

Abstract

Fe-only or FeFe hydrogenases, as they have more recently been termed, possess a uniquely organometallic enzyme active site, termed the H-cluster, where the electronic properties of an iron-sulfur cluster are tuned with distinctly non-biological ligands, carbon monoxide and cyanide. Recently, it was discovered that radical S-adenosylmethionine enzymes were involved in active hydrogenase expression. In the current work, we present a mechanistic scheme for hydrogenase H-cluster biosynthesis in which both carbon monoxide and cyanide ligands can be derived from the decomposition of a glycine radical. The ideas presented have broader implications in the context of the prebiotic origin of amino acids.

A glycyl free radical as the precursor in the synthesis of carbon monoxide and cyanide by the [FeFe]‐hydrogenase maturase HydG

“…We can conclude that, at variance with what was proposed earlier [33], the HydG-mediated generation of initial CO and CN À precursors does not require metal-based catalysis. The latter is only required for CO synthesis.…”

The CO and CN− ligands to the active site Fe in [NiFe]‐hydrogenase of Escherichia coli have different metabolic origins

“…Sawers unpublished results). Glycine has been proposed as the direct metabolic precursor for both the cyanide and CO ligands to [FeFe]-hydrogenases [24].…”

The role of the maturase HydG in [FeFe]‐hydrogenase active site synthesis and assembly

“…Intriguingly, the GTPase activity of this enzyme was not required for active site transfer to hydrogenase. Peters et al have also hypothesized that the diatomic CO and CN ligands are made from glycine although this activity was not assigned to any maturase in particular [29]. Our own structural studies of HydE have shown that this protein has three, evenly spaced, anion-binding sites in a large cavity, inside the (ab) 8 barrel [27].…”