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Characterizing Strain Variation in Engineered E. coli Using a Multi-Omics-Based Workflow

  • Author(s): Brunk, E
  • George, KW
  • Alonso-Gutierrez, J
  • Thompson, M
  • Baidoo, E
  • Wang, G
  • Petzold, CJ
  • McCloskey, D
  • Monk, J
  • Yang, L
  • O'Brien, EJ
  • Batth, TS
  • Martin, HG
  • Feist, A
  • Adams, PD
  • Keasling, JD
  • Palsson, BO
  • Lee, TS
  • et al.
Abstract

© 2016 Elsevier Inc. 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.

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