Biochemistry of Methyl-Coenzyme M Reductase: The Nickel Metalloenzyme that Catalyzes the Final Step in Synthesis and the First Step in Anaerobic Oxidation of the Greenhouse Gas Methane

Abstract

Methane, the major component of natural gas, has been in use in human civilization since ancient times as a source of fuel and light. Methanogens are responsible for synthesis of most of the methane found on Earth. The enzyme responsible for catalyzing the chemical step of methanogenesis is methyl-coenzyme M reductase (MCR), a nickel enzyme that contains a tetrapyrrole cofactor called coenzyme F430, which can traverse the Ni(I), (II), and (III) oxidation states. MCR and methanogens are also involved in anaerobic methane oxidation. This review describes structural, kinetic, and computational studies aimed at elucidating the mechanism of MCR. Such studies are expected to impact the many ramifications of methane in our society and environment, including energy production and greenhouse gas warming.

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

“…Similarly, siroheme, an Fe-containing isobacteriochlorin, acts as a prosthetic group in the six-electron reduction of either sulfite or nitrite in assimilatory sulfite and nitrite reductase. Coenzyme F 430 , a yellow-colored nickel-containing modified tetrapyrrole, plays an essential role in the final step in methanogenesis in the enzyme methyl coenzyme M (CoM) reductase (2). Heme d 1 , which is technically not a heme but an Fe-containing dioxoisobacteriochlorin, is a prosthetic group in the cytochrome cd 1 nitrite reductase (3).…”

Biocatalysts for methane conversion: big progress on breaking a small substrate

“…The mMCR catalytic cycle begins with F 430 in the reduced Ni(I) form, MCR red1 , and it is known that methyl-SCoM, the methyl donor, binds first followed by CoBSH, the electron donor, yielding the CoBS-SCoM heterodisulfide and methane [25,46]. Following binding of methyl-SCoM to the electron paramagnetic resonance (EPR)-active MCR red1 state, two possible Ni-bound intermediates have been proposed, an EPR-active methyl-Ni(III) species (mechanism I) and an EPR-silent Ni(II)-thiolate (mechanism II) (Figure 3) [14,25,29]. Using a truncated CoBSH analog (CoB 6 SH) that decreases the reaction rate, this intermediate has been trapped and characterized [29].…”

“…Moreover, since methane can be produced from waste feedstocks via methanogenesis, Bio-GTL has the potential to be a renewable energy technology [13]. The only enzymes known to catalyze biological methane conversions are methyl-coenzyme M reductases (MCRs) and methane monooxygenases (MMOs) [14–16]. …”

“…MCRs catalyze anaerobic methane conversions whereas MMOs catalyze aerobic methane oxidation [14–16]. Methanogenic MCR (mMCR) catalyzes the final step of methane synthesis in methanogens using a nickel tetrapyrrole active site (F 430 ) to couple reductive demethylation of methyl-coenzyme M (methyl-SCoM) to the oxidation of coenzyme B (CoBSH), resulting in the formation of the CoBS-SCoM heterodisulfide and methane (Figures 1B, 2A) [17].…”

“…Major accomplishments in the field include identification of their active sites, determination of their crystal structures, and elucidation of key catalytic intermediates [14,15,24–29]. Their suitability for Bio-GTL applications has been recently reviewed in depth [6,30–34].…”