ABSTRACT: BACKGROUND: Yarrowia lipolytica is an oleaginous yeast which has emerged as an important microorganism for several biotechnological processes, such as the production of organic acids, lipases and proteases. It is also considered a good candidate for single-cell oil production. Although some of its metabolic pathways are well studied, its metabolic engineering is hindered by the lack of a genome-scale model that integrates the current knowledge about its metabolism. RESULTS: Combining in silico tools and expert manual curation, we have produced an accurate genome-scale metabolic model for Y. lipolytica. Using a scaffold derived from a functional metabolic model of the well-studied but phylogenetically distant yeast S. cerevisiae, we mapped conserved reactions, rewrote gene associations, added species-specific reactions and inflected specialized copies of scaffold reactions to account for species-specific expansion of protein families. We used physiological measures obtained under lab conditions to validate our predictions. CONCLUSIONS: Y. lipolytica iNL895represents the first well-annotated metabolic model of an oleaginous yeast, providing a reference for future metabolic improvement, and a starting point for the metabolic reconstruction of other species in the Yarrowia clade and other oleaginous yeasts.
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