ArticleMicrobial cell factories2018
Metabolome analysis-based design and engineering of a metabolic pathway in Corynebacterium glutamicum to match rates of simultaneous utilization of D-glucose and L-arabinose.
Article in Microbial cell factories, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 29 citations in OpenAlex.
- Draft genome and physiological characterization of a newly isolated L-arabinose-utilizing Corynebacterium glutamicum CS176.Scientific reports · 2026Article
- Streamlined identification of strain engineering targets for bioprocess improvement using metabolic pathway enrichment analysis.Scientific reports · 2023Article
- Current advances for omics-guided process optimization of microbial manufacturing.Bioresources and bioprocessing · 2023Review
- Design and construction of microbial cell factories based on systems biology.Synthetic and systems biotechnology · 2023Review
- Metabolic Engineering of Microorganisms to Produce Pyruvate and Derived Compounds.Molecules (Basel, Switzerland) · 2023Review
- Global Cellular Metabolic Rewiring Adapts Corynebacterium glutamicum to Efficient Nonnatural Xylose Utilization.Applied and environmental microbiology · 2022Article
- Metabolomics-driven strain improvement: A mini review.Frontiers in molecular biosciences · 2022Review
- Enhanced production of γ-amino acid 3-amino-4-hydroxybenzoic acid by recombinant Corynebacterium glutamicum under oxygen limitation.Microbial cell factories · 2021Article
- Absolute Quantification of the Central Carbon Metabolome in Eight Commonly Applied Prokaryotic and Eukaryotic Model Systems.Metabolites · 2020Article
- Substrate-dependent cluster density dynamics of Corynebacterium glutamicum phosphotransferase system permeases.Molecular microbiology · 2019Article
- Recent Advances of L-ornithine Biosynthesis in Metabolically EngineeredFrontiers in bioengineering and biotechnology · 2019Review
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6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundL-Arabinose is the second most abundant component of hemicellulose in lignocellulosic biomass, next to D-xylose. However, few microorganisms are capable of utilizing pentoses, and catabolic genes and operons enabling bacterial utilization of pentoses are typically subject to carbon catabolite repression by more-preferred carbon sources, such as D-glucose, leading to a preferential utilization of D-glucose over pentoses. In order to simultaneously utilize both D-glucose and L-arabinose at the same rate, a modified metabolic pathway was rationally designed based on metabolome analysis.
resultsCorynebacterium glutamicum ATCC 31831 utilized D-glucose and L-arabinose simultaneously at a low concentration (3.6 g/L each) but preferentially utilized D-glucose over L-arabinose at a high concentration (15 g/L each), although L-arabinose and D-glucose were consumed at comparable rates in the absence of the second carbon source. Metabolome analysis revealed that phosphofructokinase and pyruvate kinase were major bottlenecks for D-glucose and L-arabinose metabolism, respectively. Based on the results of metabolome analysis, a metabolic pathway was engineered by overexpressing pyruvate kinase in combination with deletion of araR, which encodes a repressor of L-arabinose uptake and catabolism. The recombinant strain utilized high concentrations of D-glucose and L-arabinose (15 g/L each) at the same consumption rate. During simultaneous utilization of both carbon sources at high concentrations, intracellular levels of phosphoenolpyruvate declined and acetyl-CoA levels increased significantly as compared with the wild-type strain that preferentially utilized D-glucose. These results suggest that overexpression of pyruvate kinase in the araR deletion strain increased the specific consumption rate of L-arabinose and that citrate synthase activity becomes a new bottleneck in the engineered pathway during the simultaneous utilization of D-glucose and L-arabinose.
conclusionsMetabolome analysis identified potential bottlenecks in D-glucose and L-arabinose metabolism and was then applied to the following rational metabolic engineering. Manipulation of only two genes enabled simultaneous utilization of D-glucose and L-arabinose at the same rate in metabolically engineered C. glutamicum. This is the first report of rational metabolic design and engineering for simultaneous hexose and pentose utilization without inactivating the phosphotransferase system.
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