Characterizing Strain Variation in Engineered E. coli Using a Multi-Omics-Based Workflow
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Characterizing Strain Variation in Engineered E. coli Using a Multi-Omics-Based Workflow. / Brunk, Elizabeth; George, Kevin W; Alonso-Gutierrez, Jorge; Thompson, Mitchell; Baidoo, Edward; Wang, George; Petzold, Christopher J; McCloskey, Douglas; Monk, Jonathan; Yang, Laurence; O'Brien, Edward J; Batth, Tanveer S.; Martin, Hector Garcia; Feist, Adam; Adams, Paul D; Keasling, Jay D; Palsson, Bernhard O; Lee, Taek Soon.
In: Cell Systems, Vol. 2, No. 5, 2016, p. 335-346.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Characterizing Strain Variation in Engineered E. coli Using a Multi-Omics-Based Workflow
AU - Brunk, Elizabeth
AU - George, Kevin W
AU - Alonso-Gutierrez, Jorge
AU - Thompson, Mitchell
AU - Baidoo, Edward
AU - Wang, George
AU - Petzold, Christopher J
AU - McCloskey, Douglas
AU - Monk, Jonathan
AU - Yang, Laurence
AU - O'Brien, Edward J
AU - Batth, Tanveer S.
AU - Martin, Hector Garcia
AU - Feist, Adam
AU - Adams, Paul D
AU - Keasling, Jay D
AU - Palsson, Bernhard O
AU - Lee, Taek Soon
N1 - Copyright © 2016 Elsevier Inc. All rights reserved.
PY - 2016
Y1 - 2016
N2 - Understanding the complex interactions that occur between heterologous and native biochemical pathways represents a major challenge in metabolic engineering and synthetic biology. We present a workflow that integrates metabolomics, proteomics, and genome-scale models of Escherichia coli metabolism to study the effects of introducing a heterologous pathway into a microbial host. This workflow incorporates complementary approaches from computational systems biology, metabolic engineering, and synthetic biology; provides molecular insight into how the host organism microenvironment changes due to pathway engineering; and demonstrates how biological mechanisms underlying strain variation can be exploited as an engineering strategy to increase product yield. As a proof of concept, we present the analysis of eight engineered strains producing three biofuels: isopentenol, limonene, and bisabolene. Application of this workflow identified the roles of candidate genes, pathways, and biochemical reactions in observed experimental phenomena and facilitated the construction of a mutant strain with improved productivity. The contributed workflow is available as an open-source tool in the form of iPython notebooks.
AB - Understanding the complex interactions that occur between heterologous and native biochemical pathways represents a major challenge in metabolic engineering and synthetic biology. We present a workflow that integrates metabolomics, proteomics, and genome-scale models of Escherichia coli metabolism to study the effects of introducing a heterologous pathway into a microbial host. This workflow incorporates complementary approaches from computational systems biology, metabolic engineering, and synthetic biology; provides molecular insight into how the host organism microenvironment changes due to pathway engineering; and demonstrates how biological mechanisms underlying strain variation can be exploited as an engineering strategy to increase product yield. As a proof of concept, we present the analysis of eight engineered strains producing three biofuels: isopentenol, limonene, and bisabolene. Application of this workflow identified the roles of candidate genes, pathways, and biochemical reactions in observed experimental phenomena and facilitated the construction of a mutant strain with improved productivity. The contributed workflow is available as an open-source tool in the form of iPython notebooks.
U2 - 10.1016/j.cels.2016.04.004
DO - 10.1016/j.cels.2016.04.004
M3 - Journal article
C2 - 27211860
VL - 2
SP - 335
EP - 346
JO - Cell Systems
JF - Cell Systems
SN - 2405-4712
IS - 5
ER -
ID: 204046309