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 - The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment - page 138

A major focus has been aimed at MCR because it catalyzes the rate-limiting step
in methane formation and oxidation. It has been a long-term goal to identify and
characterize each catalytic intermediate in the MCR reaction mechanism. Besides
uncovering a novel bioinorganic mechanism, this information has important social,
economic and environmental ramifications. This knowledge could lead to the
development of biomimetic models that could serve as catalysts for highly efficient
fuel production. By understanding MCR, we will significantly increase control over
production of one of the most used and widely important fuels.
It is only recently that researchers have developed the ability to characterize the
intermediates in the MCR catalytic cycle. Most spectroscopic studies require a
highly homogeneous enzyme that is upwards of 80% in its active state; furthermore,
intermediates must accumulate to similarly high percentages. Over the decades of
study of MCR, the fraction of active enzyme has risen from less than 1% to nearly
100%. The use of substrate analogs has allowed transient intermediates that barely
accumulate to be trapped in relatively high yield.
Given that methods have been developed to obtain high amounts of active
enzyme, all the weapons in the arsenal of the spectroscopist and mechanistic
enzymologist can be launched at solving the MCR mechanism. Determination of
the rate constants for each of the steps in the mechanism should be achievable as
well as characterization of each of the intermediates.
Computational studies are having an important impact on studies of the enzyme
and these studies can be benchmarked with appropriate experimental data. Genetic
systems have been developed that should be poised to make variants of active-site
residues that are proposed to be mechanistically important.
There is much optimism for future studies of MCR. Yet, challenges remain.
For example, although methods have been developed to generate, stabilize and
crystallize the active state of MCR, to my knowledge, no X-ray beam line in the
world is currently able to retain the Ni(I) state during data collection. This is a
significant problem that is likely to also be affecting our interpretations of the
structures of other O 2 -sensitive metalloenzymes. The problem is just more easily
identified in MCR because the oxidation of MCR is easier to follow by simply
observing the change in color of the crystals, from green to a bright yellow color as
crystals are mounted and data collection begins.
Studying anaerobic methane oxidation by MCR is as important as understanding
methane formation. This is because methane is widely available and could serve as
an important liquid fuel [ 106 , 107 ]. In the chemical industry, methane is used to
produce synthesis gas (syngas, a mixture of CO and H 2 ) and as a fuel for electricity
generation. Methane is also used as a vehicle fuel in the form of compressed (CNG)
or liquid (LNG) natural gas, especially in Asia and South America. The current
state-of-the-art process for the conversion of natural gas to liquid fuels utilizes
Fischer-Tropsch chemistry, which is limited by high capital costs and low conver-
sion efficiencies. A biotechnological process based on enzymatic methane oxida-
tion could provide a platform for avoiding the high costs of gas storage and
distribution and combine high energy density with broad compatibility across all
modes of transportations. To achieve such a goal, it is important to use the various