Increasing L-homoserine production in Escherichia coli by engineering the central metabolic pathways

Abstract

l-homoserine is an important functional amino acid. Based on the system metabolic engineering strategy, the key genes in the central metabolic pathway of Escherichia coli W3110 were engineered to construct the strain for l-homoserine production. To construct an engineered strain with high yield of l-homoserine, the work was carried out from the following aspects: (1) Disrupt the competitive and degradative pathways of l-homoserine, and the l-homoserine was initially accumulated with a titer of 0.2 g/L; (2) Exploring the effect of weakening TCA cycle, modification of the glyoxylate branch, and reduction of the pyruvate synthesis for l-homoserine synthesis. The concentration of l-homoserine in the final recombinant strain LJL12 reached a titer of 3.2 g/L at shake flask and 35.8 g/L in fed-batch fermentation, showing a high l-homoserine production capacity (0.82 g/L/h). The study provides a well research foundation for l-homoserine production with the capacity for industrial application.

Keywords: Central metabolic pathways; Escherichia coli; Metabolic engineering; l-Homoserine.