ArticleMicrobial cell factories2015
Systems analysis of methylerythritol-phosphate pathway flux in E. coli: insights into the role of oxidative stress and the validity of lycopene as an isoprenoid reporter metabolite.
Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 24 citations in OpenAlex.
- A versatile CRISPR-associated transposases-mediated toolkit for transcriptional regulation library.Nucleic acids research · 2026Article
- Systematic CRISPRi screening reveals genetic modulators ofbioRxiv : the preprint server for biology · 2026Article
- Strategies for Metabolic Engineering ofMolecules (Basel, Switzerland) · 2026Review
- YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway ofInternational journal of molecular sciences · 2022Article
- Metabolic EngineeringMolecules (Basel, Switzerland) · 2020Review
- High density cultivation for efficient sesquiterpenoid biosynthesis in Synechocystis sp. PCC 6803.Scientific reports · 2020Article
- Adaptation of hydroxymethylbutenyl diphosphate reductase enables volatile isoprenoid production.eLife · 2020Article
- Investigation of the methylerythritol 4-phosphate pathway for microbial terpenoid production through metabolic control analysis.Microbial cell factories · 2019Article
- Start-Stop Assembly: a functionally scarless DNA assembly system optimized for metabolic engineering.Nucleic acids research · 2019Article
- Chasing bacterial chassis for metabolic engineering: a perspective review from classical to non-traditional microorganisms.Microbial biotechnology · 2019Review
- In silico model-guided identification of transcriptional regulator targets for efficient strain design.Microbial cell factories · 2018Article
- Review
- Overexpression of the primary sigma factor geneMetabolic engineering communications · 2017Article
- Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems.Beilstein journal of organic chemistry · 2017Review
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6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh-throughput screening methods assume that the output measured is representative of changes in metabolic flux toward the desired product and is not affected by secondary phenotypes. However, metabolic engineering can result in unintended phenotypes that may go unnoticed in initial screening. The red pigment lycopene, a carotenoid with antioxidant properties, has been used as a reporter of isoprenoid pathway flux in metabolic engineering for over a decade. Lycopene production is known to vary between wild-type Escherichia coli hosts, but the reasons behind this variation have never been fully elucidated.
resultsIn an examination of six E. coli strains we observed that strains also differ in their capacity for increased lycopene production in response to metabolic engineering. A combination of genetic complementation, quantitative SWATH proteomics, and biochemical analysis in closely-related strains was used to examine the mechanistic reasons for variation in lycopene accumulation. This study revealed that rpoS, a gene previously identified in lycopene production association studies, exerts its effect on lycopene accumulation not through modulation of pathway flux, but through alteration of cellular oxidative status. Specifically, absence of rpoS results in increased accumulation of reactive oxygen species during late log and stationary phases. This change in cellular redox has no effect on isoprenoid pathway flux, despite the presence of oxygen-sensitive iron-sulphur cluster enzymes and the heavy redox requirements of the methylerythritol phosphate pathway. Instead, decreased cellular lycopene in the ΔrpoS strain is caused by degradation of lycopene in the presence of excess reactive oxygen species.
conclusionsOur results demonstrate that lycopene is not a reliable indicator of isoprenoid pathway flux in the presence of oxidative stress, and suggest that caution should be exercised when using lycopene as a screening tool in genome-wide metabolic engineering studies. More extensive use of systems biology for strain analysis will help elucidate such unpredictable side-effects in metabolic engineering projects.
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