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.
journal_name
Cell Systjournal_title
Cell systemsauthors
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 TSdoi
10.1016/j.cels.2016.04.004subject
Has Abstractpub_date
2016-05-25 00:00:00pages
335-46issue
5eissn
2405-4712issn
2405-4720pii
S2405-4712(16)30112-0journal_volume
2pub_type
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