Genome scale metabolic reconstruction and hypothesis testing in the methanogenic archaeon Methanosarcina acetivorans C2A
Benedict, Matthew N.
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https://hdl.handle.net/2142/24509
Description
Title
Genome scale metabolic reconstruction and hypothesis testing in the methanogenic archaeon Methanosarcina acetivorans C2A
Author(s)
Benedict, Matthew N.
Issue Date
2011-05-25T14:25:28Z
Director of Research (if dissertation) or Advisor (if thesis)
Price, Nathan D.
Department of Study
Chemical & Biomolecular Engr
Discipline
Chemical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(s)
Methanosarcina acetivorans
Metabolic reconstruction
Flux balance analysis
Methanogen
Biofuels
Global Warming
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 implications of this organism’s unique metabolism, we have constructed and manually curated a genome-scale metabolic model, iMB744, accounting for 744 of the 4540 predicted
protein coding genes (16%) in the M. acetivorans genome. The reconstruction effort has identified key knowledge gaps and differences in the peripheral metabolism 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. Flux balance analysis was used to probe the mechanisms and energetics of byproduct formation and growth on carbon monoxide, and the nature of the reaction catalyzed by the soluble heterodisulfide reductase HdrABC in M. acetivorans. This work highlights the great utility of constraint-based modeling for identifying feasible solutions to biological questions and provides insights into the workings of the cell at the genome scale.
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