Genome-scale metabolic reconstruction and hypothesis testing in the methanogenic archaeon Methanosarcina acetivorans C2A

Matthew N. Benedict, Matthew C. Gonnerman, William W. Metcalf, Nathan D. Price

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)855-865
Number of pages11
JournalJournal of bacteriology
Volume194
Issue number4
DOIs
StatePublished - Feb 2012

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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