ArticleBiotechnology for biofuels2019
Flow-cytometry-based physiological characterisation and transcriptome analyses reveal a mechanism for reduced cell viability in yeast engineered for increased lipid content.
Article in Biotechnology for biofuels, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Discovery of thienopyrimidine analog G-18 as a novel anti-trichomonal agent.International journal for parasitology. Drugs and drug resistance · 2026Article
- Oleaginous fungi: a promising source of biofuels and nutraceuticals with enhanced lipid production strategies.Archives of microbiology · 2024Review
- Metabolic Engineering Strategies for Improved Lipid Production and Cellular Physiological Responses in YeastJournal of fungi (Basel, Switzerland) · 2022Review
- Toward fine-tuned metabolic networks in industrial microorganisms.Synthetic and systems biotechnology · 2020Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
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Abstract
backgroundYeast has been the focus of development of cell biofactories for the production of lipids and interest in the field has been driven by the need for sustainably sourced lipids for use in a broad range of industrial applications. Previously, we reported a metabolic engineering strategy for enhanced lipid production in yeast which delivered high per-cell lipid but with low cell growth and compromised physiology. To investigate the relationship between lipid engineering and cellular physiological responses and to identify further metabolic engineering targets, we analysed transcriptomes and measured cell physiology parameters in engineered strains.
resultsIn the engineering strategy, the central carbon pathway was reprogrammed to provide more precursors for lipid production and lipid accumulation and sequestration steps were enhanced through the expression of heterologous genes. Genes coding for enzymes within the pentose phosphate, beta-oxidation pathways, ATP and NADPH biosynthesis had lower transcript levels in engineered cells. Meanwhile, flow-cytometry analysis of fluorescent-dye stained cells showed the highest reactive oxygen species (ROS) levels and mitochondrial membrane potential (Δψm) in cells with the highest lipid content, supporting the known relationship between mitochondrial activity and ROS generation. High intracellular ROS and low membrane integrity were not ameliorated by application of antioxidants.
conclusionsThe limited intracellular energy supplies and the unbalanced redox environment could be regarded as targets for further lipid engineering, similarly for native lipid accumulation genes that were upregulated. Thus, lipid pathway engineering has an important effect on the central carbon pathway, directing these towards lipid production and sacrificing the precursors, energy and cofactor supply to satisfy homeostatic metabolic requirements.
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