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- Achcar, F., et al.
(author)
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The Silicon Trypanosome: A Test Case of Iterative Model Extension in Systems Biology
- 2014
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In: Advances in Microbial Physiology. - : Elsevier. - 0065-2911. - 9780128001431 ; 64, s. 115-143
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Book chapter (other academic/artistic)abstract
- The African trypanosome, Ttypanosoma brucei, is a unicellular parasite causing African Trypanosomiasis (sleeping sickness in humans and nagana in animals). Due to some of its unique properties, it has emerged as a popular model organism in systems biology. A predictive quantitative model of glycolysis in the bloodstream form of the parasite has been constructed and updated several times. The Silicon Trypanosome is a project that brings together modellers and experimentalists to improve and extend this core model with new pathways and additional levels of regulation. These new extensions and analyses use computational methods that explicitly take different levels of uncertainty into account. During this project, numerous tools and techniques have been developed for this purpose, which can now be used for a wide range of different studies in systems biology.
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| 2. |
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| 3. |
- Ledesma-Amaro, R., et al.
(author)
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Genome Scale Metabolic Modeling of the Riboflavin Overproducer Ashbya gossypii
- 2014
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In: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 111:6, s. 1191-1199
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Journal article (peer-reviewed)abstract
- Ashbya gossypii is a filamentous fungus that naturally overproduces riboflavin, or vitamin B2. Advances in genetic and metabolic engineering of A. gossypii have permitted the switch from industrial chemical synthesis to the current biotechnological production of this vitamin. Additionally, A. gossypii is a model organism with one of the smallest eukaryote genomes being phylogenetically close to Saccharomyces cerevisiae. It has therefore been used to study evolutionary aspects of bakers' yeast. We here reconstructed the first genome scale metabolic model of A. gossypii, iRL766. The model was validated by biomass growth, riboflavin production and substrate utilization predictions. Gene essentiality analysis of the A. gossypii model in comparison with the S. cerevisiae model demonstrated how the whole-genome duplication event that separates the two species has led to an even spread of paralogs among all metabolic pathways. Additionally, iRL766 was used to integrate transcriptomics data from two different growth stages of A. gossypii, comparing exponential growth to riboflavin production stages. Both reporter metabolite analysis and in silico identification of transcriptionally regulated enzymes demonstrated the important involvement of beta-oxidation and the glyoxylate cycle in riboflavin production. Biotechnol. Bioeng. 2014;111: 1191-1199.
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