L-Serine overproduction with minimization of by-product synthesis by engineered Corynebacterium glutamicum.

Abstract

The direct fermentative production of L-serine by Corynebacterium glutamicum from sugars is attractive. However, superfluous by-product accumulation and low L-serine productivity limit its industrial production on large scale. This study aimed to investigate metabolic and bioprocess engineering strategies towards eliminating by-products as well as increasing L-serine productivity. Deletion of alaT and avtA encoding the transaminases and introduction of an attenuated mutant of acetohydroxyacid synthase (AHAS) increased both L-serine production level (26.23g/L) and its productivity (0.27g/L/h). Compared to the parent strain, the by-products L-alanine and L-valine accumulation in the resulting strain were reduced by 87% (from 9.80 to 1.23g/L) and 60% (from 6.54 to 2.63g/L), respectively. The modification decreased the metabolic flow towards the branched-chain amino acids (BCAAs) and induced to shift it towards L-serine production. Meanwhile, it was found that corn steep liquor (CSL) could stimulate cell growth and increase sucrose consumption rate as well as L-serine productivity. With addition of 2g/L CSL, the resulting strain showed a significant improvement in the sucrose consumption rate (72%) and the L-serine productivity (67%). In fed-batch fermentation, 42.62g/L of L-serine accumulation was achieved with a productivity of 0.44g/L/h and yield of 0.21g/g sucrose, which was the highest production of L-serine from sugars to date. The results demonstrated that combined metabolic and bioprocess engineering strategies could minimize by-product accumulation and improve L-serine productivity.