title: Omic data from evolved E. coli are consistent with computed optimal growth from genome-scale models.
abstract: After hundreds of generations of adaptive evolution at exponential growth, Escherichia coli grows as predicted using flux balance analysis (FBA) on genome-scale metabolic models (GEMs). However, it is not known whether the predicted pathway usage in FBA solutions is consistent with gene and protein expression in the wild-type and evolved strains. Here, we report that >98% of active reactions from FBA optimal growth solutions are supported by transcriptomic and proteomic data. Moreover, when E. coli adapts to growth rate selective pressure, the evolved strains upregulate genes within the optimal growth predictions, and downregulate genes outside of the optimal growth solutions. In addition, bottlenecks from dosage limitations of computationally predicted essential genes are overcome in the evolved strains. We also identify regulatory processes that may contribute to the development of the optimal growth phenotype in the evolved strains, such as the downregulation of known regulons and stringent response suppression. Thus, differential gene and protein expression from wild-type and adaptively evolved strains supports observed growth phenotype changes, and is consistent with GEM-computed optimal growth states.
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, CA 92093-0412, USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Lewis
authors.forename: Kim K
authors.initials: KK
authors.lastname: Hixson
authors.forename: Tom M
authors.initials: TM
authors.lastname: Conrad
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lerman
authors.forename: Pep
authors.initials: P
authors.lastname: Charusanti
authors.forename: Ashoka D
authors.initials: AD
authors.lastname: Polpitiya
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Adkins
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schramm
authors.forename: Samuel O
authors.initials: SO
authors.lastname: Purvine
authors.forename: Daniel
authors.initials: D
authors.lastname: Lopez-Ferrer
authors.forename: Karl K
authors.initials: KK
authors.lastname: Weitz
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Rainer
authors.initials: R
authors.lastname: König
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Bernhard Ø
authors.initials: BØ
authors.lastname: Palsson
mesh_terms: D000222:Adaptation, Physiological; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D023281:Genomics; D005838:Genotype; D055432:Metabolomics; D008954:Models, Biological; D010641:Phenotype; D040901:Proteomics; D015203:Reproducibility of Results; D049490:Systems Biology
chemical_list: D001426:Bacterial Proteins