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Modeling and Expanding Metabolism Through Uncharted Biochemistries

Speaker: Costas Maranas, Pennsylvania State University
Series: CBE Departmental Seminars
Location: Elgin Room (E-Quad A224)
Date/Time: Wednesday, February 14, 2018, 4:00 p.m. - 5:00 p.m.

Metabolism is defined as the full complement of chemical transformations in living systems. In many biotechnological applications an organism must be endowed with additional metabolic capabilities. To support this goal, we introduced computational tools for constructing thermodynamically feasible, carbon and energy efficient, overall conversion stoichiometries by globally assessing all possible co-reactant/products combinations. Protein engineering, either de novo or through directed evolution, can expand upon the parts-list available for constructing pathways by re-purposing existing enzymes for novel conversions. However, minimizing the use of novel steps and combining them with existing reactions has remained so far elusive.  In response to this unmet need, we developed novoStoic, which allows for seamlessly blending known reactions with de novo steps to construct atom and energy balanced pathways using reaction atom mapping information. Atom tracking through reactions also enables metabolic flux elucidation at a genome-scale revealing how the assumptions implied by core metabolic models may propagate in the inference of internal metabolic fluxes. Finally, we will highlight ongoing efforts that make use of multiple flux datasets of deletion mutants to robustly parameterize kinetic models that approach genome-scale for E. coli and other microbes. We will conclude by offering insight and lessons gained from the application of these tools on a variety of bioproduction challenges.