Metabolic engineering of Corynebacterium glutamicum for improved l-arginine synthesis by enhancing NADPH supply

  • Milin Zhan
  • Baojun Kan
  • Jinjun Dong
  • Guochao Xu
  • Ruizhi Han
  • Ye NiEmail author
Fermentation, Cell Culture and Bioengineering - Original Paper


Corynebacterium glutamicum SNK 118 was metabolically engineered with improved l-arginine titer. Considering the crucial role of NADPH level in l-arginine production, pntAB (membrane-bound transhydrogenase) and ppnK (NAD+ kinase) were co-expressed to increase the intracellular NADPH pool. Expression of pntAB exhibited significant effects on NADPH supply and l-arginine synthesis. Furthermore, argR and farR, encoding arginine repressor ArgR and transcriptional regulator FarR, respectively, were removed from the genome of C. glutamicum. The competitive branch pathway gene ldh was also deleted. Eventually, an engineered C. glutamicum JML07 was obtained for l-arginine production. Fed-batch fermentation in 5-L bioreactor employing strain JML07 allowed production of 67.01 g L−1l-arginine with productivity of 0.89 g L−1 h−1 and yield of 0.35 g g−1 glucose. This study provides a productive l-arginine fermentation strain and an effective cofactor manipulating strategy for promoting the biosynthesis of NADPH-dependent metabolites.


Corynebacterium glutamicum NADPH NADP+ transhydrogenase NAD+ kinase l-Arginine 



This work was supported by National Natural Science Foundation of China (31601463), National First-class Discipline Program of Light Industry Technology and Engineering (LITE2018-07), Six Talent Peaks Project of Jiangsu Province (2015-SWYY-008), the Program of Introducing Talents of Discipline to Universities (111-2-06), and the Collaborative Innovation Center of Jiangsu Modern Industrial Fermentation. We are grateful to Prof. Xiaoyuan Wang (Jiangnan University, China) for kind assistance on construction of C. glutamicum strains.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

10295_2018_2103_MOESM1_ESM.xlsx (10 kb)
Supplementary material 1 (XLSX 10 kb)


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Copyright information

© Society for Industrial Microbiology and Biotechnology 2018

Authors and Affiliations

  1. 1.Key Laboratory of Industrial Biotechnology, Ministry of Education, School of BiotechnologyJiangnan UniversityWuxiChina
  2. 2.Key Laboratory of Guangxi BiorefineryNanningChina

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