title: 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 (26.23 g/L) and its productivity (0.27 g/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 1.23 g/L) and 60 % (from 6.54 to 2.63 g/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 2 g/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, 42.62 g/L of L-serine accumulation was achieved with a productivity of 0.44 g/L/h and yield of 0.21 g/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.
authors.affiliation: School of Pharmaceutics Science, Jiangnan University, Wuxi, 214122, People's Republic of China.
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Zhu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuchang
authors.initials: Y
authors.lastname: Luo
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Shi
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000409:Alanine / Q000378:metabolism; D050260:Carbohydrate Metabolism; D048230:Corynebacterium glutamicum / Q000378:metabolism*; D005285:Fermentation; D017353:Gene Deletion; D060847:Metabolic Engineering; D064688:Metabolic Flux Analysis; D011995:Recombination, Genetic; D012694:Serine / Q000378:metabolism*; D014633:Valine / Q000378:metabolism; D003313:Zea mays / Q000378:metabolism
chemical_list: D012694:Serine; D014633:Valine; D000409:Alanine