CO and CN- syntheses by [FeFe]-hydrogenase maturase HydG are catalytically differentiated events

Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):104-9. doi: 10.1073/pnas.1515842113. Epub 2015 Dec 22.


The synthesis and assembly of the active site [FeFe] unit of [FeFe]-hydrogenases require at least three maturases. The radical S-adenosyl-l-methionine HydG, the best characterized of these proteins, is responsible for the synthesis of the hydrogenase CO and CN(-) ligands from tyrosine-derived dehydroglycine (DHG). We speculated that CN(-) and the CO precursor (-):CO2H may be generated through an elimination reaction. We tested this hypothesis with both wild type and HydG variants defective in second iron-sulfur cluster coordination by measuring the in vitro production of CO, CN(-), and (-):CO2H-derived formate. We indeed observed formate production under these conditions. We conclude that HydG is a multifunctional enzyme that produces DHG, CN(-), and CO at three well-differentiated catalytic sites. We also speculate that homocysteine, cysteine, or a related ligand could be involved in Fe(CO)x(CN)y transfer to the HydF carrier/scaffold.

Keywords: CO/CN synthesis; FeFe hydrogenase; HydG maturase; formate; radical SAM enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon Monoxide / chemical synthesis*
  • Catalysis
  • Catalytic Domain
  • Cyanides / chemical synthesis*
  • Cysteine / chemistry
  • Desulfovibrio desulfuricans / enzymology
  • Homocysteine / chemistry
  • Hydrogenase / chemistry*
  • Hydrogenase / genetics
  • Iron-Sulfur Proteins / chemistry*
  • Iron-Sulfur Proteins / genetics
  • Ligands
  • Protein Structure, Secondary
  • S-Adenosylmethionine / chemistry
  • Tyrosine / chemistry


  • Cyanides
  • Iron-Sulfur Proteins
  • Ligands
  • Homocysteine
  • Tyrosine
  • S-Adenosylmethionine
  • Carbon Monoxide
  • iron hydrogenase
  • Hydrogenase
  • Cysteine