Impaired oxidative stress and sulfur assimilation contribute to acid tolerance of Corynebacterium glutamicum

  • Ning Xu
  • Hongfang Lv
  • Liang Wei
  • Yuan Liang
  • Jiansong Ju
  • Jun Liu
  • Yanhe Ma
Applied microbial and cell physiology


The industrial organism Corynebacterium glutamicum is often subjected to acid stress during large-scale fermentation for the production of bio-based chemicals. The capacity of the cells to thrive in acidic environments is a prerequisite for achieving high product yields. In this study, we obtained an acid-adapted strain using an adaptive laboratory evolution strategy. Physiological characterizations revealed that the adapted strain achieved improved cell viability after acid-stress challenge, with a higher cytoplasmic pHin level, a lower intracellular reactive oxygen species (ROS), and an enhanced morphological integrity of the cells, when compared to those of the original control strain. Transcriptome analysis indicated that several important cellular processes were altered in the adapted strain, including sulfur metabolism, iron transport, and central metabolic pathways. Further research displayed that KatA and Dps cooperatively mediated intracellular ROS scavenging, which was required for resistance to low-pH stress in C. glutamicum. Furthermore, the repression of sulfur assimilation by the McbR regulator also contributed to the improvement of acid-stress tolerance. Moreover, two copper chaperone genes cg1328 and cg3292 were found to be involved in promoting cell survival under acid-stress conditions. Finally, a new recombinant C. glutamicum strain with enhanced acid tolerance was generated by the combined overexpression of katA, dps, mcbR, and cg1328, showing 18.4 ± 2.5% higher biomass yields than the wild-type strain under acid-stress conditions. These findings will provide new insights into the understanding and genetic improvement of acid tolerance in C. glutamicum.


C. glutamicum Adaptive laboratory evolution Acid resistance Oxidative stress Sulfur assimilation 



We are grateful to Prof. Masayuki Inui (Research Institute of Innovative Technology for the Earth, Japan) for generously providing plasmids.


This study was supported by the National Natural Science Foundation of China (No. 31500044), the Natural Science Foundation of Tianjin (No. 17JCQNJC09600, No. 17JCYBJC24000), the Tianjin Science and Technology Project (15PTCYSY00020), the Foundation of Hebei Educational Committee (ZD2017047) and the “Hundred Talents Program” of the Chinese Academy of Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2018_9585_MOESM1_ESM.pdf (430 kb)
ESM 1 (PDF 429 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ning Xu
    • 1
  • Hongfang Lv
    • 2
  • Liang Wei
    • 1
  • Yuan Liang
    • 1
  • Jiansong Ju
    • 2
  • Jun Liu
    • 1
    • 3
  • Yanhe Ma
    • 1
  1. 1.Tianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin Airport Economic AreaPeople’s Republic of China
  2. 2.College of Life SciencesHebei Normal UniversityShijiazhuangPeople’s Republic of China
  3. 3.Key Laboratory of Systems Microbial BiotechnologyChinese Academy of SciencesTianjinPeople’s Republic of China

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