title: Biosynthesis of the [FeFe] Hydrogenase H Cluster: A Central Role for the Radical SAM Enzyme HydG.
abstract: Hydrogenase enzymes catalyze the rapid and reversible interconversion of H2 with protons and electrons. The active site of the [FeFe] hydrogenase is the H cluster, which consists of a [4Fe-4S]H subcluster linked to an organometallic [2Fe]H subcluster. Understanding the biosynthesis and catalytic mechanism of this structurally unusual active site will aid in the development of synthetic and biological hydrogenase catalysts for applications in solar fuel generation. The [2Fe]H subcluster is synthesized and inserted by three maturase enzymes-HydE, HydF, and HydG-in a complex process that involves inorganic, organometallic, and organic radical chemistry. HydG is a member of the radical S-adenosyl-l-methionine (SAM) family of enzymes and is thought to play a prominent role in [2Fe]H subcluster biosynthesis by converting inorganic Fe(2+), l-cysteine (Cys), and l-tyrosine (Tyr) into an organometallic [(Cys)Fe(CO)2(CN)](-) intermediate that is eventually incorporated into the [2Fe]H subcluster. In this Forum Article, the mechanism of [2Fe]H subcluster biosynthesis is discussed with a focus on how this key [(Cys)Fe(CO)2(CN)](-) species is formed. Particular attention is given to the initial metallocluster composition of HydG, the modes of substrate binding (Fe(2+), Cys, Tyr, and SAM), the mechanism of SAM-mediated Tyr cleavage to CO and CN(-), and the identification of the final organometallic products of the reaction.
authors.affiliation: Department of Chemistry, University of California, Davis , Davis, California 95616, United States.
authors.forename: Daniel L M
authors.initials: DL
authors.lastname: Suess
authors.affiliation: Department of Chemistry, University of California, Davis , Davis, California 95616, United States.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Kuchenreuther
authors.forename: Liliana
authors.initials: L
authors.lastname: De La Paz
authors.forename: James R
authors.initials: JR
authors.lastname: Swartz
authors.affiliation: Department of Chemistry, University of California, Davis , Davis, California 95616, United States.
authors.forename: R David
authors.initials: RD
authors.lastname: Britt
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D002384:Catalysis; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000235:genetics; D006864:Hydrogenase / Q000737:chemistry*; D007506:Iron-Sulfur Proteins / Q000737:chemistry*; D020592:Shewanella / Q000201:enzymology* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007506:Iron-Sulfur Proteins; C118830:iron hydrogenase; D006864:Hydrogenase