Multi-objective computational simulation to improve the strain for overproduction of biochemical in Escherichia coli

Abstract

There are too many combinatorial gene knock-out targets to achieve the overproduction of desired biochemicals in Escherichia coli. However, researchers cannot perform every experiment to identify the best combination of gene knock-out targets. Flux balance analysis (FBA) optimizes a specific objective function under pseudo-steady state based on the stoichiometry of metabolic reactions. In order to incorporate the physiological characteristics of the organisms under gene knock-out conditions, various methods such as minimization of metabolic adjustment (MOMA) and regulatory on/off minimization (ROOM) were developed. However, to improve a strain for biochemical production, the organism should be investigated from diverse sides simultaneously. In this respect, we propose a new approach called the flux scanning with compromised objective fluxes (FSCOF) that optimizes multi-objective functions.