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

Ma, Yuechao; Ma, Qian; Cui, Yi; Du, Lihong; Xie, Xiulan; Chen, Ning

doi:10.1007/s13213-018-1431-2

Cited by 11 publications

(7 citation statements)

References 28 publications

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“…Carbon was ready to re-enter into glycolysis from PPP to generate pyruvate. And the transcriptional level of genes relating to carboxylation of PEP and pyruvate and the formation of acety l-CoA were both upregulated [20]. While, due to the lack of enough sampling points, the whole pictures of metabolism differences among three strains were not easy to capture.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Comparative metabolomic analysis reveals different evolutionary mechanisms for branched-chain amino acids production

Zhang

et al. 2019

Bioprocess Biosyst Eng

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Evolution is a powerful tool for the breeding of microorganisms, while the connection between the changes of intracellular metabolism and different evolution directions is still unclear, which once clarified, will greatly expand the application of evolutionary engineering. We aim to clarify the correlation between metabolism changes and evolution directions in two Corynebacterium glutamicum strains for l-valine and l-leucine overproducing originated from the same parental strain by repeated random mutagenesis and selection. GC-MS metabolomics was performed to identify and quantify intracellular metabolites of the evolved and wild-type C. glutamicum strains. Time-series comparison of the fermentation processes was performed. The metabolism differences of three strains mainly exist in central carbon metabolism and the stress-resisting modes. C. glutamicum XV developed an overall "pyruvate-saving" mode for l-valine synthesis, and adopted a trehalose accumulating strategy to resist environmental stresses. C. glutamicum CP depended on an enhanced "pyruvate-producing" mode, together with certain "pyruvate-saving" strategies, for efficient l-leucine synthesis, and accumulated proline, myinositol, and inositol as the stress-resisting measure. These elaborate regulation strategies could be used in future metabolic engineering, making evolution more informative and applicable. KeywordsBranched-chain amino acid • Corynebacterium glutamcium • Metabolomics • Multivariate statistical analysis * Xixian Xie

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Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Comparative metabolomic analysis reveals different evolutionary mechanisms for branched-chain amino acids production

Zhang

et al. 2019

Bioprocess Biosyst Eng

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“…Analysis of strains producing BCAAs using genomics, transcriptomics, proteomics, and metabolomics could reveal significant information for further host modification to maximize BCAAs production. A comparison of intracellular metabolites and BCAAs production by wild-type C. glutamicum , C. glutamicum XV (producing l -valine), and C. glutamicum CP (producing l -leucine) [ 89 ] revealed a more active pentose phosphate pathway in the XV or CP strains than the wild type, indicating that these strains could produce more NADPH than the wild type. C. glutamicum XV and CP were obtained via multiple rounds of random mutagenesis [ 65 ], and these two strains are accessible at the China General Microbiological Culture Collection Center with the identifiers of CGMCC11425 (CP) and CGMCC 1.15672 (XV), respectively [ 89 ].…”

Section: Bioinformatics Analysis Of Strains Producing Bcaasmentioning

confidence: 99%

“…A comparison of intracellular metabolites and BCAAs production by wild-type C. glutamicum , C. glutamicum XV (producing l -valine), and C. glutamicum CP (producing l -leucine) [ 89 ] revealed a more active pentose phosphate pathway in the XV or CP strains than the wild type, indicating that these strains could produce more NADPH than the wild type. C. glutamicum XV and CP were obtained via multiple rounds of random mutagenesis [ 65 ], and these two strains are accessible at the China General Microbiological Culture Collection Center with the identifiers of CGMCC11425 (CP) and CGMCC 1.15672 (XV), respectively [ 89 ]. The transcription of most genes in l -valine and l -leucine biosynthetic pathways is up-regulated in the XV and CP strains [ 89 ].…”

Section: Bioinformatics Analysis Of Strains Producing Bcaasmentioning

confidence: 99%

“…C. glutamicum XV and CP were obtained via multiple rounds of random mutagenesis [ 65 ], and these two strains are accessible at the China General Microbiological Culture Collection Center with the identifiers of CGMCC11425 (CP) and CGMCC 1.15672 (XV), respectively [ 89 ]. The transcription of most genes in l -valine and l -leucine biosynthetic pathways is up-regulated in the XV and CP strains [ 89 ]. A subsequent comparison of the three strains by time-series metabolomics identified metabolic differences mainly found in central carbon metabolism and stress resistance.…”

Section: Bioinformatics Analysis Of Strains Producing Bcaasmentioning

confidence: 99%

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Metabolic engineering of Corynebacterium glutamicum for producing branched chain amino acids

Zheng

Chen

et al. 2021

Microb Cell Fact

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Background Branched chain amino acids (BCAAs) are widely applied in the food, pharmaceutical, and animal feed industries. Traditional chemical synthetic and enzymatic BCAAs production in vitro has been hampered by expensive raw materials, harsh reaction conditions, and environmental pollution. Microbial metabolic engineering has attracted considerable attention as an alternative method for BCAAs biosynthesis because it is environmentally friendly and delivers high yield. Main text Corynebacterium glutamicum (C. glutamicum) possesses clear genetic background and mature gene manipulation toolbox, and has been utilized as industrial host for producing BCAAs. Acetohydroxy acid synthase (AHAS) is a crucial enzyme in the BCAAs biosynthetic pathway of C. glutamicum, but feedback inhibition is a disadvantage. We therefore reviewed AHAS modifications that relieve feedback inhibition and then investigated the importance of AHAS modifications in regulating production ratios of three BCAAs. We have comprehensively summarized and discussed metabolic engineering strategies to promote BCAAs synthesis in C. glutamicum and offer solutions to the barriers associated with BCAAs biosynthesis. We also considered the future applications of strains that could produce abundant amounts of BCAAs. Conclusions Branched chain amino acids have been synthesized by engineering the metabolism of C. glutamicum. Future investigations should focus on the feedback inhibition and/or transcription attenuation mechanisms of crucial enzymes. Enzymes with substrate specificity should be developed and applied to the production of individual BCAAs. The strategies used to construct strains producing BCAAs provide guidance for the biosynthesis of other high value-added compounds.

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“…For example, the genes that are involved in PPP and TCA pathways, and the key genes for biosynthesis of L-valine were found to be upregulated in L-valine higher yield strain, C. glutamicum-VWB1 [ 37 ]. Ma and colleagues demonstrated that the upregulation of gene encoding aminotransferase might benefit the synthesis of L-valine and cause the significant decrease of byproducts in L-valine-producing mutant C. glutamicum XV (Table 1 ) [ 71 ].…”

Section: Approaches Based On System Metabolic Engineeringmentioning

confidence: 99%

Engineering of microbial cells for L-valine production: challenges and opportunities

et al. 2021

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L-valine is an essential amino acid that has wide and expanding applications with a suspected growing market demand. Its applicability ranges from animal feed additive, ingredient in cosmetic and special nutrients in pharmaceutical and agriculture fields. Currently, fermentation with the aid of model organisms, is a major method for the production of L-valine. However, achieving the optimal production has often been limited because of the metabolic imbalance in recombinant strains. In this review, the constrains in L-valine biosynthesis are discussed first. Then, we summarize the current advances in engineering of microbial cell factories that have been developed to address and overcome major challenges in the L-valine production process. Future prospects for enhancing the current L-valine production strategies are also discussed.

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

Cited by 11 publications

References 28 publications

Comparative metabolomic analysis reveals different evolutionary mechanisms for branched-chain amino acids production

Comparative metabolomic analysis reveals different evolutionary mechanisms for branched-chain amino acids production

Metabolic engineering of Corynebacterium glutamicum for producing branched chain amino acids

Engineering of microbial cells for L-valine production: challenges and opportunities

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