L-lysine production by systems metabolic engineering of an NADPH auto-regulated Corynebacterium glutamicum

• Published in: Bioresource technology 2023-11, Vol.387, p.129701-129701, Article 129701
• Main Authors: Liu, Jie, Ou, Ying, Xu, Jian-Zhong, Rao, Zhi-Ming, Zhang, Wei-Guo
• Format: Article
• Language: English
• Subjects: Corynebacterium glutamicum; L-lysine; NADPH; Systems metabolic engineering; Transcriptional regulator
• ISSN: 0960-8524; 1873-2976
• DOI: 10.1016/j.biortech.2023.129701

[Display omitted] •Genomic analysis of the L-lysine-producing mutant.•Metabolic engineering to improve carbon utilization, ATP supply, and transport.•Construction of a promoter library responsive to L-lysine concentration.•Dynamic optimization of the NADPH pool based on a lysine-responsive promoter. Here, the systems metabolic engineering of L-lysine-overproducing Corynebacterium glutamicum is described to create a highly efficient microorganism producer. The key chromosomal mutations associated with L-lysine synthesis were identified based on whole-genome sequencing. The carbon flux was subsequently redirected into the L-lysine synthesis pathway and increased the availability of energy and product transport systems required for L-lysine synthesis. In addition, a promoter library sensitive to intracellular L-lysine concentration was constructed and applied to regulate the NADPH pool dynamically. In the fed-batch fermentation experiment, the L-lysine titer of the final engineered strain was 223.4 ± 6.5 g/L. This study is the first to improve L-lysine production by enhancing ATP supply and NADPH self-regulation to improve the intracellular environment.