ArticleApplied and environmental microbiology2013
Platform engineering of Corynebacterium glutamicum with reduced pyruvate dehydrogenase complex activity for improved production of L-lysine, L-valine, and 2-ketoisovalerate.
Article in Applied and environmental microbiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 105 citations in OpenAlex.
- Metabolic engineering ofSynthetic and systems biotechnology · 2027Article
- Metabolic engineering strategies for sustainable de novo isobutylamine production by Corynebacterium glutamicum.Biotechnology for biofuels and bioproducts · 2026Article
- Valine overproduction inMetabolic engineering communications · 2026Article
- Production of α-ketoisovalerate with whey powder by systemic metabolic engineering of Klebsiella oxytoca.Microbial cell factories · 2024Article
- Branched-chain amino acids: physico-chemical properties, industrial synthesis and role in signaling, metabolism and energy production.Amino acids · 2024Review
- Recent Advances in Metabolic Engineering for the Biosynthesis of Phosphoenol Pyruvate-Oxaloacetate-Pyruvate-Derived Amino Acids.Molecules (Basel, Switzerland) · 2024Review
- Article
- Metabolic Engineering of Microorganisms to Produce Pyruvate and Derived Compounds.Molecules (Basel, Switzerland) · 2023Review
- System metabolic engineering ofFrontiers in bioengineering and biotechnology · 2023Article
- Evaluation of Metabolic Engineering Strategies on 2-Ketoisovalerate Production by Escherichia coli.Applied and environmental microbiology · 2022Article
- Differential Amino Acid Uptake and Depletion in Mono-Cultures and Co-Cultures ofMicroorganisms · 2022Article
- Blocking the 2,3-butanediol synthesis pathway of Klebsiella pneumoniae resulted in L-valine production.World journal of microbiology & biotechnology · 2022Article
- Expressing 2-keto acid pathway enzymes significantly increases photosynthetic isobutanol production.Microbial cell factories · 2022Article
- Metabolic engineering of Corynebacterium glutamicum for producing branched chain amino acids.Microbial cell factories · 2021Review
- Pyruvate Production by Escherichia coli by Use of Pyruvate Dehydrogenase Variants.Applied and environmental microbiology · 2021Article
- Application of RecET-Cre/loxP system in Corynebacterium glutamicum ATCC14067 for L-leucine production.Biotechnology letters · 2021Article
- Comparison of l-tyrosine containing dipeptides reveals maximum ATP availability for l-prolyl-l-tyrosine in CHO cells.Engineering in life sciences · 2020Article
- Inducible Expression Systems Based on Xenogeneic Silencing and Counter-Silencing and Design of a Metabolic Toggle Switch.ACS synthetic biology · 2020Article
- Systematic identification and elimination of flux bottlenecks in the aldehyde production pathway of Synechococcus elongatus PCC 7942.Metabolic engineering · 2020Article
- Rational modification of the carbon metabolism of Corynebacterium glutamicum to enhance L-leucine production.Journal of industrial microbiology & biotechnology · 2020Article
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9 authors at 3 institutions in 1 country.
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Abstract
Exchange of the native Corynebacterium glutamicum promoter of the aceE gene, encoding the E1p subunit of the pyruvate dehydrogenase complex (PDHC), with mutated dapA promoter variants led to a series of C. glutamicum strains with gradually reduced growth rates and PDHC activities. Upon overexpression of the l-valine biosynthetic genes ilvBNCE, all strains produced l-valine. Among these strains, C. glutamicum aceE A16 (pJC4 ilvBNCE) showed the highest biomass and product yields, and thus it was further improved by additional deletion of the pqo and ppc genes, encoding pyruvate:quinone oxidoreductase and phosphoenolpyruvate carboxylase, respectively. In fed-batch fermentations at high cell densities, C. glutamicum aceE A16 Δpqo Δppc (pJC4 ilvBNCE) produced up to 738 mM (i.e., 86.5 g/liter) l-valine with an overall yield (YP/S) of 0.36 mol per mol of glucose and a volumetric productivity (QP) of 13.6 mM per h [1.6 g/(liter × h)]. Additional inactivation of the transaminase B gene (ilvE) and overexpression of ilvBNCD instead of ilvBNCE transformed the l-valine-producing strain into a 2-ketoisovalerate producer, excreting up to 303 mM (35 g/liter) 2-ketoisovalerate with a YP/S of 0.24 mol per mol of glucose and a QP of 6.9 mM per h [0.8 g/(liter × h)]. The replacement of the aceE promoter by the dapA-A16 promoter in the two C. glutamicum l-lysine producers DM1800 and DM1933 improved the production by 100% and 44%, respectively. These results demonstrate that C. glutamicum strains with reduced PDHC activity are an excellent platform for the production of pyruvate-derived products.
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