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Mol Syst Biol. 2006;2:2006.0004. Epub 2006 Jan 31.

Modeling methanogenesis with a genome-scale metabolic reconstruction of Methanosarcina barkeri.

Author information

1
Department of Bioengineering, University of California--San Diego, La Jolla, CA 92092-0412, USA.

Abstract

We present a genome-scale metabolic model for the archaeal methanogen Methanosarcina barkeri. We characterize the metabolic network and compare it to reconstructions from the prokaryotic, eukaryotic and archaeal domains. Using the model in conjunction with constraint-based methods, we simulate the metabolic fluxes and resulting phenotypes induced by different environmental and genetic conditions. This represents the first large-scale simulation of either a methanogen or an archaeal species. Model predictions are validated by comparison to experimental growth measurements and phenotypes of M. barkeri on different substrates. The predicted growth phenotypes for wild type and mutants of the methanogenic pathway have a high level of agreement with experimental findings. We further examine the efficiency of the energy-conserving reactions in the methanogenic pathway, specifically the Ech hydrogenase reaction, and determine a stoichiometry for the nitrogenase reaction. This work demonstrates that a reconstructed metabolic network can serve as an analysis platform to predict cellular phenotypes, characterize methanogenic growth, improve the genome annotation and further uncover the metabolic characteristics of methanogenesis.

PMID:
16738551
PMCID:
PMC1681478
DOI:
10.1038/msb4100046
[Indexed for MEDLINE]
Free PMC Article

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