(375e) Metabolic Reconstruction of An Archaeon Methanogen: Methanosarcina Acetivorans

In this talk, we put forth a computational workflow for the reconstruction of genome-scale models. The procedure is demonstrated for the archaeon methanogen Methanosarcina acetivorans that has the largest sequenced genome in the archaeal domain. Methanogens are key players in the carbon cycle for about 70% of the annual biological methane production. In carrying out an initial reconstruction, we took advantage of the existing metabolic reconstruction for a closely related methanogen, M. barkeri that has a genome that is 80% the size of M. acetivorans. Although there is a significant overlap in their genotypes, M. acetivorans possesses unique methanogenesis pathways and has unique substrate utilizing capabilities. We first used sequence similarity searches to assemble an initial model for M. acetivorans that is comprised of 630 reactions and accounts for 720 genes. Specifically, we imposed a stringent e-value cutoff of 10-30 for inclusion of a gene/protein/reaction association to the model. Additionally, we incorporated updated annotations made available as part of an ongoing effort at the University of Maryland (carried out in the Sowers Lab at the Center for Marine Biotechnology) for M. acetivorans. Using this information in combination with a comprehensive search for metabolic annotations, we were able to include 110 additional genes and 66 reactions in the initial draft of the metabolic model. A systematic procedure to curate this initial reconstruction using connectivity, gene essentiality data and substrate utilization potential is underway.