Skip to main content
eScholarship
Open Access Publications from the University of California

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

  • Author(s): 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
  • et al.
Abstract

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View