k-OptForce: Integrating Kinetics with Flux Balance Analysis for Strain Design

• DOI: 10.1371/journal.pcbi.1003487
• Publication Date: 2014-02-20T22:03:25Z
• Authors: Anupam Chowdhury; Ali R. Zomorrodi; Costas D. Maranas
• Keywords: Flux Balance Analysis; Metabolic Engineering

Computational strain design protocols aim at the system-wide identification of intervention strategies for enhanced production biochemicals in microorganisms. Existing approaches relying solely on stoichiometry and rudimentary constraint-based regulation overlook effects metabolite concentrations substrate-level enzyme while identifying metabolic interventions. In this paper, we introduce k-OptForce, which integrates available kinetic descriptions steps with stoichiometric models to sharpen prediction improving bio-production a chemical interest. It enables minimal set interventions comprised both enzymatic parameter changes (for reactions kinetics) reaction flux only information). Application k-OptForce overproduction L-serine E. coli triacetic acid lactone (TAL) S. cerevisiae revealed that identified tend cause less dramatic rearrangements distribution so as not violate concentration bounds. some cases incorporation information leads need additional expressions render stoichiometry-only derived infeasible by violating bounds, whereas other impart favor target product thereby requiring fewer direct A sensitivity analysis shows required number can be significantly affected changing imposed bounds concentrations. Furthermore, was capable finding non-intuitive aiming alleviating inhibition key enzymes order enhance towards interest, cannot captured stoichiometry-alone analysis. This study paves way integrated elucidating capturing regulatory effects.