title: The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase.
abstract: Methyl-coenzyme M reductase, the rate-limiting enzyme in methanogenesis and anaerobic methane oxidation, is responsible for the biological production of more than 1 billion tons of methane per year. The mechanism of methane synthesis is thought to involve either methyl-nickel(III) or methyl radical/Ni(II)-thiolate intermediates. We employed transient kinetic, spectroscopic, and computational approaches to study the reaction between the active Ni(I) enzyme and substrates. Consistent with the methyl radical-based mechanism, there was no evidence for a methyl-Ni(III) species; furthermore, magnetic circular dichroism spectroscopy identified the Ni(II)-thiolate intermediate. Temperature-dependent transient kinetics also closely matched density functional theory predictions of the methyl radical mechanism. Identifying the key intermediate in methanogenesis provides fundamental insights to develop better catalysts for producing and activating an important fuel and potent greenhouse gas.
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-0606, USA.
authors.forename: Thanyaporn
authors.initials: T
authors.lastname: Wongnate
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-0606, USA.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Sliwa
authors.affiliation: Physical Sciences Division, Pacific Northwest National Laboratory, Post Office Box 999, K1-83, Richland, WA 99352, USA.
authors.forename: Bojana
authors.initials: B
authors.lastname: Ginovska
authors.affiliation: Physical Sciences Division, Pacific Northwest National Laboratory, Post Office Box 999, K1-83, Richland, WA 99352, USA.
authors.forename: Dayle
authors.initials: D
authors.lastname: Smith
authors.affiliation: Department of Chemistry and Department of Biophysics, University of Michigan, Ann Arbor, MI 48109-1055, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Wolf
authors.affiliation: Department of Chemistry and Department of Biophysics, University of Michigan, Ann Arbor, MI 48109-1055, USA.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Lehnert
authors.affiliation: Physical Sciences Division, Pacific Northwest National Laboratory, Post Office Box 999, K1-83, Richland, WA 99352, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Raugei
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-0606, USA. sragsdal@umich.edu.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Ragsdale
mesh_terms: D055162:Biocatalysis; D020134:Catalytic Domain; D004789:Enzyme Activation; D006860:Hydrogen Bonding; D007700:Kinetics; D008697:Methane / Q000096:biosynthesis*; D017013:Methanobacteriaceae / Q000201:enzymology*; D056004:Molecular Dynamics Simulation; D009532:Nickel / Q000737:chemistry; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods; D013696:Temperature
chemical_list: D009532:Nickel; D010088:Oxidoreductases; C021572:methyl coenzyme M reductase; D008697:Methane