title: Genome scale metabolic modeling of the riboflavin overproducer Ashbya gossypii.
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.
authors.affiliation: Departamento de Microbiología y Genética, Metabolic Engineering Group, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ledesma-Amaro
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Kerkhoven
authors.forename: José Luis
authors.initials: JL
authors.lastname: Revuelta
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics*; D003198:Computer Simulation; D055169:Eremothecium / Q000235:genetics* / Q000378:metabolism*; D053263:Gene Regulatory Networks; D016681:Genome, Fungal; D008954:Models, Biological; D012256:Riboflavin / Q000096:biosynthesis*; D049490:Systems Biology
chemical_list: D012256:Riboflavin
keywords: Ashbya gossypii; Eremothecium; genome-scale metabolic model; microbial biotechnology; riboflavin; systems metabolic engineering