Genome-Scale Constraint-Based Metabolic Modeling and Analysis of Cryptoccocus Curvatus

Cryptococcus curvatus, also known as Cutaneotrichosporon curvatus, an oleaginous fungus, is gaining attention due to its ability to use a wide range of carbon sources and its ability to accumulate more than 60% lipid in its biomass. In this study we constructed a genome-scale metabolic model for C.curvatus that can help to understand and achieve higher yield of lipid production.

A draft model was constructed using the scaffold-based method by Loira et al (2012). The draft model was extensively curated based on published data and literature with special emphasis on lipid synthesis pathways. The model was used to simulate growth on different carbon sources. RNAseq data were obtained at C:N of 16:1 and 8:5 with two replicates for each condition. These expression data were integrated into the model to study lipid synthesis in C.curvatus.

The current version of the model has 831 genes, 1436 metabolites and 1679 reactions distribute in 11 compartments. The growth predictions are highly consistent with experimental data. However, the initial model was not able to predict differences in lipid synthesis at varying nitrogen concentrations. Integration of expression data will lead to improve predictions on lipid production at nitrogen abundant and nitrogen depleted conditions. These results illustrate that the model can be further used to study and guide metabolic engineering for optimization of C.curvatus as a cell factory for lipid production.

References

Loira, N., Dulermo, T., Nicaud, J.-M., & Sherman, D. (2012). A genome-scale metabolic model of the lipid-accumulating yeast Yarrowia lipolytica. BMC Systems Biology, 6(1), 35. https://doi.org/10.1186/1752-0509-6-35