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Microbial 1‐butanol production: Identification of non‐native production routes and in silico engineering interventions
Author(s) -
Ranganathan Sridhar,
Maranas Costas D.
Publication year - 2010
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.201000171
Subject(s) - metabolic engineering , in silico , escherichia coli , computational biology , metabolic pathway , biochemical engineering , synthetic biology , yield (engineering) , identification (biology) , kegg , chemistry , computer science , biochemistry , biology , gene , materials science , engineering , gene expression , transcriptome , metallurgy , botany
The potential of engineering microorganisms with non‐native pathways for the synthesis of long‐chain alcohols has been identified as a promising route to biofuels. We describe computationally derived predictions for assembling pathways for the production of biofuel candidate molecules and subsequent metabolic engineering modifications that optimize product yield. A graph‐based algorithm illustrates that, by culling information from BRENDA and KEGG databases, all possible pathways that link the target product with metabolites present in the production host are identified. Subsequently, we apply our recent OptForce procedure to pinpoint reaction modifications that force the imposed product yield in Escherichia coli. We demonstrate this procedure by suggesting new pathways and genetic interventions for the overproduction of 1‐butanol using the metabolic model for Escherichia coli. The graph‐based search method recapitulates all recent discoveries based on the 2‐ketovaline intermediate and hydroxybutyryl‐CoA but also pinpointes one novel pathway through thiobutanoate intermediate that to the best of our knowledge has not been explored before.