Functional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides

The fungus Rhodosporidium toruloides can grow on substances extracted from plant matter that is inedible to humans such as corn stalks, wood pulp, and grasses. Under some growth conditions, the fungus can accumulate massive stores of hydrocarbon-rich fats and pigments. A community of scientists and engineers has begun genetically modifying R. toruloides to convert these naturally produced fats and pigments into fuels, chemicals and medicines. These could form sustainable replacements for products made from petroleum or harvested from threatened animal and plant species. Fungi, plants, animals and other eukaryotes store fat in specialized compartments called lipid droplets. The genes that control the metabolism – the production, use and storage – of fat in lipid bodies have been studied in certain eukaryotes, including species of yeast. However, R. toruloides is only distantly related to the most well-studied of these species. This means that we cannot be certain that a gene will play the same role in R. toruloides as in those species. To assemble the most comprehensive list possible of the genes in R. toruloides that affect the production, use, or storage of fat in lipid bodies, Coradetti, Pinel et al. constructed a population of hundreds of thousands of mutant fungal strains, each with its own unique DNA ‘barcode’. The effects that mutations in over 6,000 genes had on growth and fat accumulation in these fungi were measured simultaneously in several experiments. This general approach is not new, but technical limitations had, until now, restricted its use in fungi to a few species. Coradetti, Pinel et al. identified hundreds of genes that affected the ability of R. toruloides to metabolise fat. Many of these genes were related to genes with known roles in fat metabolism in other eukaryotes. Other genes are involved in different cell processes, such as the recycling of waste products in the cell. Their identification adds weight to the view that the links between these cellular processes and fat metabolism are deep and widespread amongst eukaryotes. Finally, some of the genes identified by Coradetti, Pinel et al. are not closely related to any well-studied genes. Further study of these genes could help us to understand why R. toruloides can accumulate much larger amounts of fat than most other fungi. The methods developed by Coradetti, Pinel et al. should be possible to implement in many species of fungi. As a result these techniques may eventually contribute to the development of new treatments for human fungal diseases, the protection of important food crops, and a deeper understanding of the roles various fungi play in the broader ecosystem.