Interconnected regulation of carbon catabolite repression and carbon source utilization in an oleaginous yeast

Cells must sense and respond to available nutrients to survive. Microbes evolved mechanisms to activate genes necessary to utilize a carbon source specifically when it is present. To efficiently grow in mixed carbon source environments, microbes repress genes necessary to utilize carbon sources that require substantial resources to catabolize when a simpler carbon source is present, known as carbon catabolite repression. We investigated nutrient utilization in the basidiomycete, oleaginous yeast Rhodotorula (Rhodosporidium) toruloides . R. toruloides is a saprophytic fungus that utilizes the building blocks of complex polysaccharides found in plant cell walls. A transcription factor homologous to the cellulose degradation regulator CLR-2/ClrB in Ascomycete filamentous fungi, which we named Cbr1, is required for cellobiose utilization in R. toruloides . Although the role of CLR-2/ClrB is limited to regulating expression of genes involved in cellulose and hemicellulose utilization, Cbr1 is also involved in fucose and tricarboxylic acid cycle intermediate utilization. Additionally, Cbr1 inhibits carbon catabolite repression specifically during utilization of glucose-glucose disaccharides, which may have evolved to limit the glucose-mediated repression of genes encoding proteins that cleave disaccharides into glucose. In fungi, it is thought carbon source-specific transcription factors activate genes necessary for carbon source utilization, while carbon catabolite repression is regulated by transcription factors that broadly repress all nonpreferred carbon source utilization genes when a preferred carbon source is present. Our data provide evidence for a noncanonical carbon catabolite repression mechanism and suggest transcriptional mechanisms regulating carbon catabolite repression may be less broadly conserved than previously thought.