Optimality of Microbial Metabolism with Biosynthetic Heterologous Reactions

As more of microorganisms are metabolically engineered to produce chemicals beyond their native metabolism, it has become important to systematically study the effects of introducing heterologous reactions on microbial metabolism. However, in contrast to gene knockout mutants and microorganisms under environmental perturbations, microbial metabolism with heterologous reactions has not been studied sufficiently. To this end, we use genome-scale metabolic models representing Escherichia coli strains engineered to produce 1,4-butanediol, 1,3-propanediol, and amorphadiene with previously reported ¹³C-based flux data in order to investigate effects of foreign reactions on microbial metabolism. Overall, the simulated microbial metabolism with heterologous pathways shows either very optimal or non-optimal statuses with respect to the theoretically optimal metabolic space in a strain-specific manner. This observation contrasts with wild-type and single gene knockout mutants whose metabolism tends to be slightly sub-optimal, but rather stable. Variables causing more complex effects of introducing heterologous reactions than single gene knockouts or environmental perturbations will be discussed.[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-2012-C1AAA001-2012M1A2A2026556).]