Design of homo-organic acid producing strains using multi-objective optimization

Production of homo-organic acids without byproducts is an important challenge in bioprocess engineering to minimize operation cost for separation processes. In this study, we used multi-objective optimization to design Escherichia coli strains with the goals of maximally producing target organic acids, while maintaining sufficiently high growth rate and minimizing the secretion of undesired byproducts. Homo-productions of acetic, lactic and succinic acids were targeted as examples. Engineered E. coli strains capable of producing homo-acetic and homo-lactic acids could be developed by taking this systems approach for the minimal identification of gene knockout targets. Also, failure to predict effective gene knockout targets for the homo-succinic acid production suggests that the multi-objective optimization is useful in assessing the suitability of a microorganism as a host strain for the production of a homo-organic acid. The systems metabolic engineering-based approach reported here should be applicable to the production of other industrially important organic acids. [Display omitted] •Producing homo-organic acids is critical for reducing purification costs.•Gene targets predicted from multi-objective optimization minimize byproducts.•Production of homo-acetic and lactic acids is experimentally demonstrated.•Random sampling of fluxes reveals metabolic cues for minimal byproducts.•The constructed strains can be used as base strains for further engineering.