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Open Access Highly Accessed Research article

Comparative multi-goal tradeoffs in systems engineering of microbial metabolism

David Byrne1*, Alexandra Dumitriu1 and Daniel Segrè123*

Author Affiliations

1 Bioinformatics Program, Boston University, Boston, MA, 02215, USA

2 Department of Biology, Boston University, Boston, MA, 02215, USA

3 Department of Biomedical Engineering, Boston University, Boston, MA, 02215, USA

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BMC Systems Biology 2012, 6:127  doi:10.1186/1752-0509-6-127

Published: 26 September 2012

Abstract

Background

Metabolic engineering design methodology has evolved from using pathway-centric, random and empirical-based methods to using systems-wide, rational and integrated computational and experimental approaches. Persistent during these advances has been the desire to develop design strategies that address multiple simultaneous engineering goals, such as maximizing productivity, while minimizing raw material costs.

Results

Here, we use constraint-based modeling to systematically design multiple combinations of medium compositions and gene-deletion strains for three microorganisms (Escherichia coli, Saccharomyces cerevisiae, and Shewanella oneidensis) and six industrially important byproducts (acetate, D-lactate, hydrogen, ethanol, formate, and succinate). We evaluated over 435 million simulated conditions and 36 engineering metabolic traits, including product rates, costs, yields and purity.

Conclusions

The resulting metabolic phenotypes can be classified into dominant clusters (meta-phenotypes) for each organism. These meta-phenotypes illustrate global phenotypic variation and sensitivities, trade-offs associated with multiple engineering goals, and fundamental differences in organism-specific capabilities. Given the increasing number of sequenced genomes and corresponding stoichiometric models, we envisage that the proposed strategy could be extended to address a growing range of biological questions and engineering applications.

Keywords:
Metabolism; Microorganisms; Metabolic engineering; Constraint-based modeling