ArticleApplied and environmental microbiology2012
Improvement of the redox balance increases L-valine production by Corynebacterium glutamicum under oxygen deprivation conditions.
Article in Applied and environmental microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 129 citations in OpenAlex.
- Metabolic engineering ofSynthetic and systems biotechnology · 2027Article
- Anaerobic metabolic evolution for homotypic L-valine fermentation.Nature communications · 2026Article
- Draft genome and physiological characterization of a newly isolated L-arabinose-utilizing Corynebacterium glutamicum CS176.Scientific reports · 2026Article
- Droplet based microfluidic and miniaturization at high-throughput level to screening heterologous secondary metabolites in microbes: A critical review.Biotechnology letters · 2025Review
- EngineeringBiodesign research · 2025Review
- Construction and screening of L-valine high-yieldingFrontiers in microbiology · 2025Article
- Production of α-ketoisovalerate with whey powder by systemic metabolic engineering of Klebsiella oxytoca.Microbial cell factories · 2024Article
- Productive and metabolomic consequences of arginine supplementation in sows during different gestation periods in two different seasons.Journal of animal science and biotechnology · 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
- Construction of a plasmid-free L-leucine overproducing Escherichia coli strain through reprogramming of the metabolic flux.Biotechnology for biofuels and bioproducts · 2023Article
- De novo tryptophanase-based indole production by metabolically engineered Corynebacterium glutamicum.Applied microbiology and biotechnology · 2023Article
- Rossmann-toolbox: a deep learning-based protocol for the prediction and design of cofactor specificity in Rossmann fold proteins.Briefings in bioinformatics · 2022Article
- Metabolic engineering of Corynebacterium glutamicum for producing branched chain amino acids.Microbial cell factories · 2021Review
- L-valine production in Corynebacterium glutamicum based on systematic metabolic engineering: progress and prospects.Amino acids · 2021Review
- Engineering of microbial cells for L-valine production: challenges and opportunities.Microbial cell factories · 2021Review
- Physiological characteristics of Corynebacterium glutamicum as a cell factory under anaerobic conditions.Applied microbiology and biotechnology · 2021Review
- A Myo-Inositol-Inducible Expression System forFrontiers in bioengineering and biotechnology · 2021Article
- Improvement of l-Leucine Production inInternational journal of molecular sciences · 2019Article
- Application of leucine dehydrogenase Bcd fromHeliyon · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Production of L-valine under oxygen deprivation conditions by Corynebacterium glutamicum lacking the lactate dehydrogenase gene ldhA and overexpressing the L-valine biosynthesis genes ilvBNCDE was repressed. This was attributed to imbalanced cofactor production and consumption in the overall L-valine synthesis pathway: two moles of NADH was generated and two moles of NADPH was consumed per mole of L-valine produced from one mole of glucose. In order to solve this cofactor imbalance, the coenzyme requirement for L-valine synthesis was converted from NADPH to NADH via modification of acetohydroxy acid isomeroreductase encoded by ilvC and introduction of Lysinibacillus sphaericus leucine dehydrogenase in place of endogenous transaminase B, encoded by ilvE. The intracellular NADH/NAD(+) ratio significantly decreased, and glucose consumption and L-valine production drastically improved. Moreover, L-valine yield increased and succinate formation decreased concomitantly with the decreased intracellular redox state. These observations suggest that the intracellular NADH/NAD(+) ratio, i.e., reoxidation of NADH, is the primary rate-limiting factor for L-valine production under oxygen deprivation conditions. The L-valine productivity and yield were even better and by-products derived from pyruvate further decreased as a result of a feedback resistance-inducing mutation in the acetohydroxy acid synthase encoded by ilvBN. The resultant strain produced 1,470 mM L-valine after 24 h with a yield of 0.63 mol mol of glucose(-1), and the L-valine productivity reached 1,940 mM after 48 h.
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