Genome-Scale In Silico Analysis for Enhanced Production of Succinic Acid in Zymomonas mobilis

Abstract

Presented herein is a model-driven strategy for characterizing the production capability of expression host and subsequently identifying targets for strain improvement by resorting to network structural comparison with reference strain and in silico analysis of genome-scale metabolic model. The applicability of the strategy was demonstrated by exploring the capability of Zymomonas mobilis, as a succinic acid producer. Initially, the central metabolism of Z. mobilis was compared with reference producer, Mannheimia succiniciproducens, in order to identify gene deletion targets. It was followed by combinatorial gene deletion analysis. Remarkably, resultant in silico strains suggested that knocking out pdc, ldh, and pfl genes encoding pyruvate-consuming reactions as well as the cl gene leads to fifteen-fold increase in succinic acid molar yield. The current exploratory work could be a promising support to wet experiments by providing guidance for metabolic engineering strategies and lowering the number of trials and errors.