Genome-scale metabolic modeling underscores the potential of Cutaneotrichosporon oleaginosus ATCC 20509 as a cell factory for biofuel production

Cutaneotrichosporon oleaginosus ATCC 20509 is a fast-growing oleaginous basidiomycete yeast that is able to grow in a wide range of low-cost carbon sources including crude glycerol, a byproduct of biodiesel production. When glycerol is used as a carbon source, this yeast can accumulate more than 50% lipids (w/w) with high concentrations of mono-unsaturated fatty acids. To increase our understanding of this yeast and to provide a knowledge base for further industrial use, a FAIR re-annotated genome was used to build a genome-scale, constraint-based metabolic model containing 1553 reactions involving 1373 metabolites in 11 compartments. A new description of the biomass synthesis reaction was introduced to account for massive lipid accumulation in conditions with high carbon-to-nitrogen (C/N) ratio in the media. This condition-specific biomass objective function is shown to better predict conditions with high lipid accumulation using glucose, fructose, sucrose, xylose, and glycerol as sole carbon source. Contributing to the economic viability of biodiesel as renewable fuel, C. oleaginosus ATCC 20509 can effectively convert crude glycerol waste streams in lipids as a potential bioenergy source. Performance simulations are essential to identify optimal production conditions and to develop and fine tune a cost-effective production process. Our model suggests ATP-citrate lyase as a possible target to further improve lipid production.