ArticlePloS one2016
Metabolomics Revealed an Association of Metabolite Changes and Defective Growth in Methylobacterium extorquens AM1 Overexpressing ecm during Growth on Methanol.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- A novel engineered strain of Methylorubrum extorquens for methylotrophic production of glycolic acid.Microbial cell factories · 2024Article
- Construction of Xylose-Utilizing Cyanobacterial Chassis for Bioproduction Under Photomixotrophic Conditions.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Developing methylotrophic microbial platforms for a methanol-based bioindustry.Frontiers in bioengineering and biotechnology · 2022Review
- Biomedical Applications of Biomolecules Isolated from Methanotrophic Bacteria in Wastewater Treatment Systems.Biomolecules · 2021Review
- Salt-TolerantFrontiers in microbiology · 2021Article
- Improved Salt Tolerance and Metabolomics Analysis ofFrontiers in bioengineering and biotechnology · 2020Article
- Introduction of Glyoxylate Bypass Increases Hydrogen Gas Yield from Acetate and l-Glutamate inApplied and environmental microbiology · 2019Article
- Metabolic engineering of Methylobacterium extorquens AM1 for the production of butadiene precursor.Microbial cell factories · 2018Article
- Methanol-essential growth of Escherichia coli.Nature communications · 2018Article
- Production of 3-hydroxypropionic acid in engineered Methylobacterium extorquens AM1 and its reassimilation through a reductive route.Microbial cell factories · 2017Article
- Metabolomics Investigation of an Association of Induced Features and Corresponding Fungus during the Co-culture ofFrontiers in microbiology · 2017Article
- Discovery of novel xylosides in co-culture of basidiomycetes Trametes versicolor and Ganoderma applanatum by integrated metabolomics and bioinformatics.Scientific reports · 2016Article
- Ultrahigh Pressure Processing Produces Alterations in the Metabolite Profiles of Panax ginseng.Molecules (Basel, Switzerland) · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methylobacterium extorquens AM1 is a facultative methylotroph capable of growth on both single-carbon and multi-carbon compounds. The ethylmalonyl-CoA (EMC) pathway is one of the central assimilatory pathways in M. extorquens during growth on C1 and C2 substrates. Previous studies had shown that ethylmalonyl-CoA mutase functioned as a control point during the transition from growth on succinate to growth on ethylamine. In this study we overexpressed ecm, phaA, mcmAB and found that upregulating ecm by expressing it from the strong constitutive mxaF promoter caused a 27% decrease in growth rate on methanol compared to the strain with an empty vector. Targeted metabolomics demonstrated that most of the central intermediates in the ecm over-expressing strain did not change significantly compared to the control strain; However, poly-β-hydroxybutyrate (PHB) was 4.5-fold lower and 3-hydroxybutyryl-CoA was 1.6-fold higher. Moreover, glyoxylate, a toxic and highly regulated essential intermediate, was determined to be 2.6-fold higher when ecm was overexpressed. These results demonstrated that overexpressing ecm can manipulate carbon flux through the EMC pathway and divert it from the carbon and energy storage product PHB, leading to an accumulation of glyoxylate. Furthermore, untargeted metabolomics discovered two unusual metabolites, alanine (Ala)-meso-diaminopimelic acid (mDAP) and Ala-mDAP-Ala, each over 45-fold higher in the ecm over-expressing strain. These two peptides were also found to be highly produced in a dose-dependent manner when glyoxylate was added to the control strain. Overall, this work has explained a direct association of ecm overexpression with glyoxylate accumulation up to a toxic level, which inhibits cell growth on methanol. This research provides useful insight for manipulating the EMC pathway for efficiently producing high-value chemicals in M. extorquens.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.