A genome-scale metabolic model of the lipid-accumulating yeast Yarrowia lipolytica

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 inserted 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.Y. lipolytica iNL895 represents the first well-annotated metabolic model of an oleaginous yeast, providing a base for future metabolic improvement, and a starting point for the metabolic reconstruction of other species in the Yarrowia clade and other oleaginous yeasts.Even if lipid metabolism is common to all microorganisms, we call oleaginous those that can store at least 20% of their dry mass as lipids. It is possible to find oleaginous organisms among plants, algae, bacteria and yeasts. Plants and algae are technically difficult (and controversial) to modify genetically, while oleaginous bateria present a low growth rate. On the other side, oleaginous yeasts enjoy well-developed genetic tools for their improvement and grow quickly. Also, oleaginous yeasts can accumulate up to 70% of their dry mass as lipids [1], making them the best candidates for industrial lipid production such as microbial oil for biodiesel.One of those oleaginous yeasts, Yarrowia lipolytica, normally found as a food contaminant, has been extensively studied experimentally. It is easy to modify genetically, and presents many opportunities for metabolic engineering. For example, Y. lipolytica has been used as a food supplement, given its easily modifiable lipid composition. It is also studied as a potential source of biodiesel [2-4], because lipids producedby this species are similar to vegetable oils and fats. While Y. lipolytica is a hemiascomyce