title: Metabolic network architecture and carbon source determine metabolite production costs.
abstract: Metabolism is essential to organismal life, because it provides energy and building block metabolites. Even though it is known that the biosynthesis of metabolites consumes a significant proportion of the resources available to a cell, the factors that determine their production costs remain less well understood. In this context, it is especially unclear how the nutritional environment affects the costs of metabolite production. Here, we use the amino acid metabolism of Escherichia coli as a model to show that the point at which a carbon source enters central metabolic pathways is a major determinant of individual metabolite production costs. Growth rates of auxotrophic genotypes, which in the presence of the required amino acid save biosynthetic costs, were compared to the growth rates that prototrophic cells achieved under the same conditions. The experimental results showed a strong concordance with computationally estimated biosynthetic costs, which allowed us, for the first time, to systematically quantify carbon source-dependent metabolite production costs. Thus, we demonstrate that the nutritional environment in combination with network architecture is an important but hitherto underestimated factor influencing biosynthetic costs and thus microbial growth. Our observations are highly relevant for the optimization of biotechnological processes as well as for understanding the ecology of microorganisms in their natural environments.
authors.affiliation: Research Group Theoretical Systems Biology, Friedrich Schiller University Jena, Jena, Germany.|Experimental Ecology and Evolution Research Group, Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Jena, Germany.|Research Group Medical Systems Biology, Institute for Experimental Medicine, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Waschina
authors.affiliation: Experimental Ecology and Evolution Research Group, Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Jena, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: D'Souza
authors.affiliation: Experimental Ecology and Evolution Research Group, Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kost
authors.affiliation: Research Group Theoretical Systems Biology, Friedrich Schiller University Jena, Jena, Germany.|Research Group Medical Systems Biology, Institute for Experimental Medicine, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaleta
mesh_terms: D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D001709:Biotechnology; D002244:Carbon / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics*
chemical_list: D000596:Amino Acids; D002244:Carbon; D005947:Glucose
keywords: Escherichia coli; amino acid auxotrophies; biosynthetic cost; flux balance analysis; metabolic trade-off; resource allocation problem