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Title: Designing overall stoichiometric conversions and intervening metabolic reactions

Abstract

Existing computational tools for de novo metabolic pathway assembly, either based on mixed integer linear programming techniques or graph-search applications, generally only find linear pathways connecting the source to the target metabolite. The overall stoichiometry of conversion along with alternate co-reactant (or co-product) combinations is not part of the pathway design. Therefore, global carbon and energy efficiency is in essence fixed with no opportunities to identify more efficient routes for recycling carbon flux closer to the thermodynamic limit. Here, we introduce a two-stage computational procedure that both identifies the optimum overall stoichiometry (i.e., optStoic) and selects for (non-)native reactions (i.e., minRxn/minFlux) that maximize carbon, energy or price efficiency while satisfying thermodynamic feasibility requirements. Implementation for recent pathway design studies identified non-intuitive designs with improved efficiencies. Specifically, multiple alternatives for non-oxidative glycolysis are generated and non-intuitive ways of co-utilizing carbon dioxide with methanol are revealed for the production of C 2+ metabolites with higher carbon efficiency.

Authors:
 [1];  [1]
  1. Pennsylvania State Univ., State College, PA (United States)
Publication Date:
Research Org.:
Pennsylvania State Univ., University Park, PA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1242041
Grant/Contract Number:  
SC0008091
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Chowdhury, Anupam, and Maranas, Costas D. Designing overall stoichiometric conversions and intervening metabolic reactions. United States: N. p., 2015. Web. doi:10.1038/srep16009.
Chowdhury, Anupam, & Maranas, Costas D. Designing overall stoichiometric conversions and intervening metabolic reactions. United States. doi:10.1038/srep16009.
Chowdhury, Anupam, and Maranas, Costas D. Wed . "Designing overall stoichiometric conversions and intervening metabolic reactions". United States. doi:10.1038/srep16009. https://www.osti.gov/servlets/purl/1242041.
@article{osti_1242041,
title = {Designing overall stoichiometric conversions and intervening metabolic reactions},
author = {Chowdhury, Anupam and Maranas, Costas D.},
abstractNote = {Existing computational tools for de novo metabolic pathway assembly, either based on mixed integer linear programming techniques or graph-search applications, generally only find linear pathways connecting the source to the target metabolite. The overall stoichiometry of conversion along with alternate co-reactant (or co-product) combinations is not part of the pathway design. Therefore, global carbon and energy efficiency is in essence fixed with no opportunities to identify more efficient routes for recycling carbon flux closer to the thermodynamic limit. Here, we introduce a two-stage computational procedure that both identifies the optimum overall stoichiometry (i.e., optStoic) and selects for (non-)native reactions (i.e., minRxn/minFlux) that maximize carbon, energy or price efficiency while satisfying thermodynamic feasibility requirements. Implementation for recent pathway design studies identified non-intuitive designs with improved efficiencies. Specifically, multiple alternatives for non-oxidative glycolysis are generated and non-intuitive ways of co-utilizing carbon dioxide with methanol are revealed for the production of C2+ metabolites with higher carbon efficiency.},
doi = {10.1038/srep16009},
journal = {Scientific Reports},
issn = {2045-2322},
number = ,
volume = 5,
place = {United States},
year = {2015},
month = {11}
}

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