Homo-Organic Acid Production with Minimal Byproducts through Multi-Objective Optimization of Microbial Metabolism

Minimization of byproducts during strain development is a key to reduce operation cost by facilitating separation and purification of microbial bioproducts in the downstream process. In this context, we implement strain design not only to maximize the target chemical product at a sufficiently high cellular growth rate, but also to minimize byproducts using a concept of multi-objective optimization of the production host’s metabolic model. We experimentally demonstrate this approach for productions of acetic, lactic and succinic acids in E. coli as proof-of-concept studies. E. coli strains producing homo-acetic and homo-lactic acids were constructed by knocking out a minimal number of gene targets predicted from the E. coli metabolic model. Meanwhile, gene knockout targets that enable the homo-succinic acid production were not predicted for E. coli. This prediction failure suggests that the multi-objective optimization of host’s metabolic network can be used to evaluate whether a specific microorganism is a suitable host for the production of a homo-organic acid. This systems metabolic engineering approach can be considered for the production of other industrially important chemicals.[This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation (NRF) of Korea (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557).]