Metabolic network architecture and carbon source determine metabolite production costs

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 we...

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Bibliographic Details
Published in:The FEBS journal 2016-06, Vol.283 (11), p.2149-2163
Main Authors: Waschina, Silvio, D'Souza, Glen, Kost, Christian, Kaleta, Christoph
Format: Article
Language:English
Subjects:
amino acid auxotrophies
Amino Acids - genetics
Amino Acids - metabolism
biosynthetic cost
Biotechnology
Carbon
Carbon - metabolism
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
flux balance analysis
Glucose - metabolism
Metabolic Networks and Pathways - genetics
metabolic trade‐off
Metabolism
Metabolites
resource allocation problem
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Summary: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. The biosynthesis of building block metabolites induces enormous costs to the cell by consuming a large fraction of the cell's resource budget. Here, we report a metabolic cost trade‐off in the biosynthesis of different amino acids in E. coli between different types of carbon sources. The observations are highly relevant for the optimization of biotechnological processes and for understanding the ecology of microorganisms.
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.13727