Highly efficient production of L-valine by multiplex metabolic engineering of <i>Corynebacterium glutamicum</i>.

Kuo Zhao; Jinyu Cheng; Liang Guo; Cong Gao; Wei Song; Jing WU; Jia Liu; Yadi Liu; Liming Liu; Xiulai Chen

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Highly efficient production of L-valine by multiplex metabolic engineering of Corynebacterium glutamicum.

Author: Kuo ZHAO ¹ ; Jinyu CHENG ¹ ; Liang GUO ¹ ; Cong GAO ¹ ; Wei SONG ² ; Jing WU ² ; Jia LIU ¹ ; Yadi LIU ¹ ; Liming LIU ¹ ; Xiulai CHEN ¹
Author Information

1. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China.
2. School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, Jiangsu, China.
Publication Type:Journal Article
Keywords: Corynebacterium glutamicum; L-valine; metabolic engineering; pathway optimization
MeSH: Valine; Corynebacterium glutamicum/genetics*; Metabolic Engineering; Amino Acids, Branched-Chain; Bioreactors
From: Chinese Journal of Biotechnology 2023;39(8):3253-3272
CountryChina
Language:Chinese
Abstract: As a branched chain amino acid, L-valine is widely used in the medicine and feed sectors. In this study, a microbial cell factory for efficient production of L-valine was constructed by combining various metabolic engineering strategies. First, precursor supply for L-valine biosynthesis was enhanced by strengthening the glycolysis pathway and weakening the metabolic pathway of by-products. Subsequently, the key enzyme in the L-valine synthesis pathway, acetylhydroxylate synthase, was engineered by site-directed mutation to relieve the feedback inhibition of the engineered strain. Moreover, promoter engineering was used to optimize the gene expression level of key enzymes in L-valine biosynthetic pathway. Furthermore, cofactor engineering was adopted to change the cofactor preference of acetohydroxyacid isomeroreductase and branched-chain amino acid aminotransferase from NADPH to NADH. The engineered strain C. glutamicum K020 showed a significant increase in L-valine titer, yield and productivity in 5 L fed-batch bioreactor, up to 110 g/L, 0.51 g/g and 2.29 g/(L‧h), respectively.