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The PhoPR two-component system responds to oxygen deficiency and regulates the pathways for energy supply in Corynebacterium glutamicum

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Abstract

The PhoPR two-component system, a highly conserved system in corynebacteria and mycobacteria, is involved in the cellular response to environmental stress. When analysing the transcriptomic data of Corynebacterium glutamicum strains under different dissolved oxygen (DO) levels, PhoPR was found to be the most responsive two-component system to DO changes. Here, we systematically investigated the expression of PhoPR in response to different DO levels and its impact on genes related to global regulation and energy metabolism. Using Green fluorescent protein as a reporter, we confirmed that PhoPR was significantly upregulated upon decrease of DO. Through real-time quantitative PCR and electrophoretic mobility shift assay, we found that the effector protein PhoP directly activated glxR (encoding a global regulator), pfk and gapA (encoding the glycolytic enzymes) and ctaD (encoding cytochrome c in the electron transport chain), while downregulated aceE and gltA (encoding the TCA cycle enzymes). Overexpression of phoP or phoR resulted in a decreased intracellular NAD+/NADH ratio and increased intracellular ATP level, consistent with the gene expression changes regulated by PhoP. These results reveal the PhoPR system respond to oxygen deficiency and is responsible for the regulation of pathways involved in the sustainability of the energy levels required under low oxygen conditions. Our findings in this study not only provide new insights into the adaptation pathways of C. glutamicum in response to low oxygen conditions but also identify new possible genetic targets for the construction of the new cell factories aimed toward industrial applications.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (Grant Nos. 21808082, 21878124, 22078128 and 21938004); The 111 Project (No. 111-2-06); National frst-class discipline program of Light Industry Technology and Engineering (LITE2018-24). We thank Dr. Giacomo Giacomelli and Abigail Savietto Scholz for their helpful advices on this paper.

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  1. Feng Peng and Jing Chen have contributed equally to this work.

Authors and Affiliations

  1. The Key Laboratory of Carbohydrate Chemistry and Biotechnology, School of Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Feng Peng, Jing Chen, Xiuxia Liu, Ye Li, Chunli Liu, Yankun Yang & Zhonghu Bai

  2. National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi, 214122, China

    Feng Peng, Jing Chen, Xiuxia Liu, Ye Li, Chunli Liu, Yankun Yang & Zhonghu Bai

  3. The Key Laboratory of Industrial Biotechnology, School of Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Feng Peng, Xiuxia Liu, Ye Li, Chunli Liu, Yankun Yang & Zhonghu Bai

  4. Jiangsu Provincial Research Center for Bioactive Product Processing Technology, Jiangnan University, Wuxi, 214122, China

    Feng Peng, Xiuxia Liu, Ye Li, Chunli Liu, Yankun Yang & Zhonghu Bai

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  1. Feng Peng
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Contributions

FP, XL, JC and ZB conceived and designed research. FP and JC performed the experiment and analyzed the results. YL, CL and YY contributed new methods. FP, JC, YL and XL wrote and revised the paper. All authors read and approved the final manuscript.

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Correspondence to Xiuxia Liu.

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Peng, F., Chen, J., Liu, X. et al. The PhoPR two-component system responds to oxygen deficiency and regulates the pathways for energy supply in Corynebacterium glutamicum. World J Microbiol Biotechnol 37, 160 (2021). https://doi.org/10.1007/s11274-021-03131-1

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