Biotechnology Letters

, Volume 35, Issue 5, pp 735–741 | Cite as

Modification of histidine biosynthesis pathway genes and the impact on production of l-histidine in Corynebacterium glutamicum

  • Yongsong Cheng
  • Yunjiao Zhou
  • Lei Yang
  • Chenglin Zhang
  • Qingyang Xu
  • Xixian Xie
  • Ning ChenEmail author
Original Research Paper


Histidine biosynthesis in Corynebacterium glutamicum is regulated not only by feedback inhibition by the first enzyme in the pathway, but also by repression control of the synthesis of the histidine enzymes. C. glutamicum histidine genes are located and transcribed in two unlinked loci, hisEG and hisDCB-orf1-orf2-hisHA-impA-hisFI. We constructed plasmid pK18hisDPtac to replace the native hisD promoter with the tac promoter, and overexpressed phosphoribosyl-ATP-pyrophosphohydrolase, encoded by hisE, and ATP-phosphoribosyltransferase, encoded by hisG. The l-histidine titer at 0.85 g l−1 was 80 % greater in the transformed bacterium and production of byproducts, l-alanine and l-tryptophan, was significantly decreased. However, accumulation of glutamic acid increased by 58 % (2.8 g l−1). This study represents the first attempt to substitute the histidine biosynthesis pathway promoter in the chromosome with a stronger promoter to increase histidine production.


Corynebacterium glutamicum Gene overexpression l-Histidine Promoter substitution 



This work was supported by the Tianjin Committee of Science and Technology (Grant No. 12ZCZDSY01900, 12ZXCXSY05900), and by the Program for Changjiang Scholars and Innovative Research Team in Universities (IRT 1166).

Supplementary material

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Yongsong Cheng
    • 1
  • Yunjiao Zhou
    • 1
  • Lei Yang
    • 1
  • Chenglin Zhang
    • 1
  • Qingyang Xu
    • 1
  • Xixian Xie
    • 1
  • Ning Chen
    • 1
    • 2
    Email author
  1. 1.College of Biotechnology, Tianjin University of Science & Technology, Key Laboratory of Industrial Microbiology of Education MinistryTianjinChina
  2. 2.Metabolic Engineering LaboratoryCollege of Biotechnology, Tianjin University of Science & TechnologyTianjinChina

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