Joseph R Peterson, Piyush Labhsetwar, Jeremy R Ellermeier, Petra R A Kohler,
Ankur Jain, Taekjip Ha, William W Metcalf, and Zaida Luthey-Schulten.
Towards a computational model of a methane producing archaeum.
Archaea, 2014, 2014.
(18 pages).
(PMC: PMC3960522)
PETE2014-ZLS
Progress towards a complete model of the methanogenic archaeum
Methanosarcina acetivorans is reported. We characterized size distribution of
the cells using differential interference contrast microscopy, finding them to be
ellipsoidal with mean length and width of 2.9 m and 2.3 m,
respectively, when grown on methanol and 30% smaller when grown on acetate.
We used the single molecule pull down (SiMPull) technique to measure average
copy number of the Mcr complex and ribosomes. A kinetic model for the
methanogenesis pathways based on biochemical studies and recent metabolic
reconstructions for several related methanogens is presented. In this model, 26
reactions in the methanogenesis pathways are coupled to a cell mass production
reaction that updates enzyme concentrations. RNA expression data (RNA-seq)
measured for cell cultures grown on acetate and methanol is used to estimate
relative protein production per mole of ATP consumed. The model captures the
experimentally observed methane production rates for cells growing on
methanol and is most sensitive to the number of methyl-coenzyme-M reductase
(Mcr) and methyl-tetrahydromethanopterin:coenzyme-M methyltransferase (Mtr)
proteins. A draft transcriptional regulation network based on known interactions
is proposed which we intend to integrate with the kinetic model to allow dynamic
regulation.
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