Laboratory evolution reveals a two-dimensional rate-yield tradeoff in microbial metabolism

• Published in: PLoS computational biology Vol. 15; no. 6; p. e1007066
• Main Authors: Cheng, Chuankai, O’Brien, Edward J., McCloskey, Douglas, Utrilla, Jose, Olson, Connor, LaCroix, Ryan A., Sandberg, Troy E., Feist, Adam M., Palsson, Bernhard O., King, Zachary A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2019; Public Library of Science (PLoS)
• Subjects: Adaptation; Amino acids; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bioengineering; Biology and Life Sciences; Biomass; Carbon; Complexity; Computer applications; E coli; Enzymes; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Evolution; Evolution & development; Evolution (Biology); Evolution, Molecular; Experiments; Fermentation; Funding; Gene expression; Genes; Genome, Bacterial - genetics; Genomes; Genomics; Glucose; Glucose metabolism; Glycolysis; Growth rate; Laboratories; Mathematical models; Medicine and Health Sciences; Metabolism; Microbial growth; Microbial metabolism; Microorganisms; Models, Biological; Molecular weight; Monosaccharides; Multiscale analysis; Mutation; Natural history; Overflow; Pentose; Pentose phosphate pathway; Phosphates; Physical Sciences; Proteins; Proteome - genetics; Proteome - metabolism; Proteomes; Respiration; Scale models; Software; Substrates; Systems Biology; Tradeoffs; Two dimensional analysis; Two dimensional models; Yield; United States; Denmark; La Jolla California; California; United States > US
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1007066

Growth rate and yield are fundamental features of microbial growth. However, we lack a mechanistic and quantitative understanding of the rate-yield relationship. Studies pairing computational predictions with experiments have shown the importance of maintenance energy and proteome allocation in explaining rate-yield tradeoffs and overflow metabolism. Recently, adaptive evolution experiments of Escherichia coli reveal a phenotypic diversity beyond what has been explained using simple models of growth rate versus yield. Here, we identify a two-dimensional rate-yield tradeoff in adapted E. coli strains where the dimensions are (A) a tradeoff between growth rate and yield and (B) a tradeoff between substrate (glucose) uptake rate and growth yield. We employ a multi-scale modeling approach, combining a previously reported coarse-grained small-scale proteome allocation model with a fine-grained genome-scale model of metabolism and gene expression (ME-model), to develop a quantitative description of the full rate-yield relationship for E. coli K-12 MG1655. The multi-scale analysis resolves the complexity of ME-model which hindered its practical use in proteome complexity analysis, and provides a mechanistic explanation of the two-dimensional tradeoff. Further, the analysis identifies modifications to the P/O ratio and the flux allocation between glycolysis and pentose phosphate pathway (PPP) as potential mechanisms that enable the tradeoff between glucose uptake rate and growth yield. Thus, the rate-yield tradeoffs that govern microbial adaptation to new environments are more complex than previously reported, and they can be understood in mechanistic detail using a multi-scale modeling approach.