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Transcriptomic and metabolomics analyses reveal metabolic characteristics of L-leucine- and L-valine-producing Corynebacterium glutamicum mutants

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Abstract

Industrial amino acid production strains of Corynebacterium glutamicum are usually obtained by mutagenesis. However, the genetic and metabolic characteristics and the efficient synthesis mechanism of the selected mutants are unclear. The aims of this study were (1) to determine the gene transcriptional patterns and intracellular metabolite levels of an L-leucine-producing mutant C. glutamicum CP and an L-valine-producing mutant C. glutamicum XV referring to wild type, and (2) to understand the efficient synthesis mechanism of target product of these mutants. For this purpose, transcriptomic and metabolomics analyses were combined to investigate the association between intracellular patterns and product synthesis. The high intracellular level of glucose and the low intracellular level of metabolites in the central carbon metabolism meant the glucose metabolism rate of two mutants was lower than wild type. However, the increased intracellular pentose level and gene transcription in the pentose phosphate pathway (PPP) indicated that the PPP of mutants was more active. Furthermore, the mutants showed higher intracellular level of NADPH, which was mainly generated in PPP. In the specific pathway for the synthesis of L-leucine and L-valine, the transcriptional level of most genes was upregulated in the mutants. However, the transcription of transaminase C coding gene Cgl2844 was downregulated in CP but upregulated in XV. The upregulation of Cgl2844 might benefit to the synthesis of L-valine and cause the significant decrease of intracellular level of L-alanine and L-glutamate of XV. These characteristics of the mutants provided insight into changes that could be made to systematically optimize the metabolic pathways for the production of L-leucine and L-valine.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (31470211 and 31770053), Natural Science Foundation of Tianjin (17JCQNJC09500), and Tianjin Municipal Science and Technology Commission (17YFZCSY01050).

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Author notes

  1. Yuechao Ma and Qian Ma contributed equally to this work and should be considered as co-first authors

Authors and Affiliations

  1. National and Local United Engineering Lab of Metabolic Control Fermentation Technology, Tianjin University of Science & Technology, Tianjin, 300457, People’s Republic of China

    Yuechao Ma, Qian Ma, Yi Cui, Lihong Du, Xixian Xie & Ning Chen

  2. Key Laboratory of Microbial Engineering of China Light Industry, Tianjin University of Science & Technology, Tianjin, 300457, People’s Republic of China

    Yuechao Ma, Qian Ma, Yi Cui, Lihong Du, Xixian Xie & Ning Chen

  3. College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, People’s Republic of China

    Yuechao Ma, Qian Ma, Yi Cui, Lihong Du, Xixian Xie & Ning Chen

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  1. Yuechao Ma
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  2. Qian Ma
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Correspondence to Xixian Xie or Ning Chen.

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Ma, Y., Ma, Q., Cui, Y. et al. Transcriptomic and metabolomics analyses reveal metabolic characteristics of L-leucine- and L-valine-producing Corynebacterium glutamicum mutants. Ann Microbiol 69, 457–468 (2019). https://doi.org/10.1007/s13213-018-1431-2

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  • DOI: https://doi.org/10.1007/s13213-018-1431-2

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