ArticleMetabolomics : Official journal of the Metabolomic Society2022
Metabolomics for the design of new metabolic engineering strategies for improving aerobic succinic acid production in Escherichia coli.
Article in Metabolomics : Official journal of the Metabolomic Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 22 citations in OpenAlex.
- Efficient synthesis of l-DOPA inSynthetic and systems biotechnology · 2026Article
- Prospecting technology and economic potential to produce bio-succinic acid: a review.Biotechnology reports (Amsterdam, Netherlands) · 2025Review
- Kidney Stone Disease: Epigenetic Dysregulation in Homocystinuria and Mitochondrial Sulfur Trans-Sulfuration Ablation Driven by COVID-19 Pathophysiology.Biomolecules · 2025Review
- Rising trend in the microbial fermentation for succinic acid production: a comprehensive overview on innovative approaches using versatile biological sources.Archives of microbiology · 2025Review
- Evolution-assisted engineering ofBiodesign research · 2025Article
- Effect of adaptive laboratory evolution of engineered Escherichia coli in acetate on the biosynthesis of succinic acid from glucose in two-stage cultivation.Bioresources and bioprocessing · 2024Article
- Metabolomics ofInternational journal of molecular sciences · 2023Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionGlycerol is a byproduct from the biodiesel industry that can be biotransformed by Escherichia coli to high added-value products such as succinate under aerobic conditions. The main genetic engineering strategies to achieve this aim involve the mutation of succinate dehydrogenase (sdhA) gene and also those responsible for acetate synthesis including acetate kinase, phosphate acetyl transferase and pyruvate oxidase encoded by ackA, pta and pox genes respectively in the ΔsdhAΔack-ptaΔpox (M4) mutant. Other genetic manipulations to rewire the metabolism toward succinate consist on the activation of the glyoxylate shunt or blockage the pentose phosphate pathway (PPP) by deletion of isocitrate lyase repressor (iclR) or gluconate dehydrogenase (gnd) genes on M4-ΔiclR and M4-Δgnd mutants respectively.
objectiveTo deeply understand the effect of the blocking of the pentose phosphate pathway (PPP) or the activation of the glyoxylate shunt, metabolite profiles were analyzed on M4-Δgnd, M4-ΔiclR and M4 mutants.
methodsMetabolomics was performed by FT-IR and GC-MS for metabolite fingerprinting and HPLC for quantification of succinate and glycerol.
resultsMost of the 65 identified metabolites showed lower relative levels in the M4-ΔiclR and M4-Δgnd mutants than those of the M4. However, fructose 1,6-biphosphate, trehalose, isovaleric acid and mannitol relative concentrations were increased in M4-ΔiclR and M4-Δgnd mutants. To further improve succinate production, the synthesis of mannitol was suppressed by deletion of mannitol dehydrogenase (mtlD) on M4-ΔgndΔmtlD mutant that increase ~ 20% respect to M4-Δgnd.
conclusionMetabolomics can serve as a holistic tool to identify bottlenecks in metabolic pathways by a non-rational design. Genetic manipulation to release these restrictions could increase the production of succinate.
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