| Description |
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Background: Microbial hosts offer a number of unique advantages when
used as production systems for both native and heterologous small-molecules. These
advantages include high selectivity and benign environmental impact; however, a
principal drawback is low yield and/or productivity, which limits economic viability.
Therefore a major ... read morechallenge in developing a microbial production system is to
maximize formation of a specific product while sustaining cell growth. Tools to
rationally reconfigure microbial metabolism for these potentially conflicting
objectives remain limited. Exhaustively exploring combinations of genetic
modifications is both experimentally and computationally inefficient, and can become
intractable when multiple gene deletions or insertions need to be considered.
Alternatively, the search for desirable gene modifications may be solved
heuristically as an evolutionary optimization problem. In this study, we combine a
genetic algorithm and elementary mode analysis to develop an optimization framework
for evolving metabolic networks with energetically favorable pathways for production
of both biomass and a compound of interest.
Keywords: standard change in Gibbs free energy of formation, standard
change in Gibbs free energy across a pathway/EM, standard change in Gibbs free energy
across a reaction, standard change in entropy across a pathway/EM, elementary mode,
elementary mode analysis, flux balance analysis, genetic algorithm, metabolic flux
analysis, multi-objective genetic algorithm, minimization of metabolic adjustment,
non-dominated sorting genetic algorithm-II, regulatory on/off minimization,
transcriptional regulatory network, transcriptional and
translational.
Springer Open.read less
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| Citation |
- Boghigian, Brett, Hai Shi, Kyongbum Lee, and Blaine A.
Pfeifer. "Utilizing elementary mode analysis, pathway thermodynamics, and a genetic
algorithm for metabolic flux determination and optimal metabolic network design." BMC
Systems Biology 4, no. 1 (12, 2010): 1-17.
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