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

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.