Genome-Scale Metabolic Reconstruction and Hypothesis Testing in the Methanogenic Archaeon Methanosarcina acetivorans C2A

Methanosarcina acetivorans strain C2A is a marine methanogenic archaeon notable for its substrate utilization, genetic tractability, and novel energy conservation mechanisms. To help probe the phenotypic implications of this organism's unique metabolism, we have constructed and manually curated...

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Bibliographic Details
Published in:Journal of Bacteriology 2012-02, Vol.194 (4), p.855-865
Main Authors: Benedict, Matthew N, Gonnerman, Matthew C, Metcalf, William W, Price, Nathan D
Format: Article
Language:English
Subjects:
Bacteriology
Biological and medical sciences
carbon monoxide
Carbon Monoxide - metabolism
energy conservation
Formates - metabolism
Fundamental and applied biological sciences. Psychology
Gene Knockout Techniques
genes
Genome, Archaeal
Genomes
Genotype & phenotype
Metabolic Networks and Pathways - genetics
Metabolism
Methane - metabolism
methane production
methanogens
Methanosarcina
Methanosarcina - genetics
Methanosarcina - growth & development
Methanosarcina - metabolism
Microbiology
Microorganisms
Miscellaneous
Models, Biological
Oxidoreductases - metabolism
Phenotype
prediction
Thermodynamics
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Summary:Methanosarcina acetivorans strain C2A is a marine methanogenic archaeon notable for its substrate utilization, genetic tractability, and novel energy conservation mechanisms. To help probe the phenotypic implications of this organism's unique metabolism, we have constructed and manually curated a genome-scale metabolic model of M. acetivorans, iMB745, which accounts for 745 of the 4,540 predicted protein-coding genes (16%) in the M. acetivorans genome. The reconstruction effort has identified key knowledge gaps and differences in peripheral and central metabolism between methanogenic species. Using flux balance analysis, the model quantitatively predicts wild-type phenotypes and is 96% accurate in knockout lethality predictions compared to currently available experimental data. The model was used to probe the mechanisms and energetics of by-product formation and growth on carbon monoxide, as well as the nature of the reaction catalyzed by the soluble heterodisulfide reductase HdrABC in M. acetivorans. The genome-scale model provides quantitative and qualitative hypotheses that can be used to help iteratively guide additional experiments to further the state of knowledge about methanogenesis.
ISSN:0021-9193
1098-5530
1067-8832
DOI:10.1128/JB.06040-11