Inverse metabolic engineering based on elementary mode analysis was applied to maximize the biomass yield of Escherchia coli MG1655. Elementary mode analysis was previously employed to identify among 1691 possible pathways for cell growth the most efficient pathway with maximum biomass yield. The metabolic network analysis predicted that deletion of only 6 genes reduces the number of possible elementary modes to the most efficient pathway. We have constructed a strain containing these gene deletions and we evaluated its properties in batch and in chemostat growth experiments. The results show that the theoretical predictions are closely matched by the properties of the designed strain.
Bibliographical noteFunding Information:
We would like to acknowledge the National Science Foundation (NSF) and the 3M Corporation for financial support of the project, and the Minnesota Supercomputing Institute (MSI) for using supercomputing facilities. We would also like to thank Prof. Khodursky for helping to develop the EMA relational database, Prof. Wanner for providing us the single gene knockout library of E. coli and Prof. Bond for using his HPLC system to quantify the concentration of secreted metabolites.
Copyright 2011 Elsevier B.V., All rights reserved.
- Biomass yield optimization
- Elementary (flux) mode
- Inverse metabolic engineering
- Metabolic network analysis