Multi-omics Quantification of Species Variation of Escherichia coli Links Molecular Features with Strain Phenotypes.
Escherichia coli strains are widely used in academic research and biotechnology. New technologies for quantifying strain-specific differences and their underlying contributing factors promise greater understanding of how these differences significantly impact physiology, synthetic biology, metabolic engineering, and process design. Here, we quantified strain-specific differences in seven widely used strains of E. coli (BL21, C, Crooks, DH5a, K-12 MG1655, K-12 W3110, and W) using genomics, phenomics, transcriptomics, and genome-scale modeling. Metabolic physiology and gene expression varied widely with downstream implications for productivity, product yield, and titer. These differences could be linked to differential regulatory structure. Analyzing high-flux reactions and expression of encoding genes resulted in a correlated and quantitative link between these sets, with strain-specific caveats. Integrated modeling revealed that certain strains are better suited to produce given compounds or express desired constructs considering native expression states of pathways that enable high-production phenotypes. This study yields a framework for quantitatively comparing strains in a species with implications for strain selection.
Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Jonathan M
JM
Monk
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2970 Hørsholm, Denmark.
Anna
A
Koza
Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA; Centre for Biotechnology and Bioengineering, CeBiB, University of Chile, Beauchef 850, Santiago, Chile.
Miguel A
MA
Campodonico
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2970 Hørsholm, Denmark.
Daniel
D
Machado
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2970 Hørsholm, Denmark.
Jose Miguel
JM
Seoane
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2970 Hørsholm, Denmark; Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
Bernhard O
BO
Palsson
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2970 Hørsholm, Denmark.
Markus J
MJ
Herrgård
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2970 Hørsholm, Denmark; Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA. Electronic address: afeist@ucsd.edu.
Adam M
AM
Feist
D004926:Escherichia coli; D029968:Escherichia coli Proteins; D016680:Genome, Bacterial; D023281:Genomics; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways; D010641:Phenotype
D029968:Escherichia coli Proteins
Escherichia coli; genome-scale modeling; metabolic engineering; systems biology
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