ABSTRACT:
Richards2016 - Genome-scale metabolic
reconstruction of Methanococcus maripaludis (iMR539)
This model is described in the article:
Exploring Hydrogenotrophic
Methanogenesis: a Genome Scale Metabolic Reconstruction of
Methanococcus maripaludis.
Richards MA, Lie TJ, Zhang J,
Ragsdale SW, Leigh JA, Price ND.
J. Bacteriol. 2016 Dec; 198(24):
3379-3390
Abstract:
Hydrogenotrophic methanogenesis occurs in multiple
environments, ranging from the intestinal tracts of animals to
anaerobic sediments and hot springs. Energy conservation in
hydrogenotrophic methanogens was long a mystery; only within
the last decade was it reported that net energy conservation
for growth depends on electron bifurcation. In this work, we
focus on Methanococcus maripaludis, a well-studied
hydrogenotrophic marine methanogen. To better understand
hydrogenotrophic methanogenesis and compare it with
methylotrophic methanogenesis that utilizes oxidative
phosphorylation rather than electron bifurcation, we have built
iMR539, a genome scale metabolic reconstruction that accounts
for 539 of the 1,722 protein-coding genes of M. maripaludis
strain S2. Our reconstructed metabolic network uses recent
literature to not only represent the central electron
bifurcation reaction but also incorporate vital biosynthesis
and assimilation pathways, including unique cofactor and
coenzyme syntheses. We show that our model accurately predicts
experimental growth and gene knockout data, with 93% accuracy
and a Matthews correlation coefficient of 0.78. Furthermore, we
use our metabolic network reconstruction to probe the
implications of electron bifurcation by showing its
essentiality, as well as investigating the infeasibility of
aceticlastic methanogenesis in the network. Additionally, we
demonstrate a method of applying thermodynamic constraints to a
metabolic model to quickly estimate overall free-energy changes
between what comes in and out of the cell. Finally, we describe
a novel reconstruction-specific computational toolbox we
created to improve usability. Together, our results provide a
computational network for exploring hydrogenotrophic
methanogenesis and confirm the importance of electron
bifurcation in this process.Understanding and applying
hydrogenotrophic methanogenesis is a promising avenue for
developing new bioenergy technologies around methane gas.
Although a significant portion of biological methane is
generated through this environmentally ubiquitous pathway,
existing methanogen models portray the more traditional energy
conservation mechanisms that are found in other methanogens. We
have constructed a genome scale metabolic network of
Methanococcus maripaludis that explicitly accounts for all
major reactions involved in hydrogenotrophic methanogenesis.
Our reconstruction demonstrates the importance of electron
bifurcation in central metabolism, providing both a window into
hydrogenotrophic methanogenesis and a hypothesis-generating
platform to fuel metabolic engineering efforts.
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MODEL1607200000.
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Matthew Richards 
