Cornell scientists have identified a genetic regulator that helps a species of yeast unlock energy from complex sugars, offering a possible target for disrupting disease-causing fungi. The study examined how fungi sense available nutrients and decide which carbon sources to use, a process also relevant to future biotechnology.
Researchers found that a transcription factor called Cbr1 turns on genes needed to break complex sugars into glucose in the yeast Rhodotorula toruloides. Cbr1 also bypasses a feedback system that would otherwise shut those genes down once glucose is present.
Study explains how fungi keep using complex sugars
Fungi generally prefer glucose because it is an easily accessible source of carbon. When glucose is available, fungal cells normally repress genes that help them process carbon sources requiring more energy.
That response creates a problem when glucose is locked inside a larger sugar. Cellobiose, for example, contains two glucose molecules, but the presence of newly released glucose can trigger the cell to suppress the very genes needed to continue breaking cellobiose apart.
The Cornell team found that Cbr1 interrupts that negative feedback loop. It activates genes involved in processing complex sugars and blocks the mechanism that would repress those genes, allowing the yeast to keep accessing carbon that remains in its environment.
Researchers used transcriptomics to measure gene activity across the R. toruloides genome and in engineered strains of the yeast. That comparison allowed them to identify genes controlled by Cbr1, including one that produces an enzyme for breaking down cellobiose.
The study found that Cbr1 performs the same regulatory role with other complex sugars made from two glucose molecules. The results were published Sept. 1 in the journal PLOS Biology.
Findings could guide biotechnology and treatments
R. toruloides can accumulate lipids equal to as much as 70% of its biomass. Researchers are trying to engineer the yeast so those fats can be directed into useful products such as biofuels and environmentally friendly plastics.
The organism can consume breakdown products from plant cells, meaning it could be fed grasses grown on marginal land or agricultural waste rather than material intended for food. A clearer understanding of its nutrient-sensing system could make that engineering more precise.
The same biological mechanisms may also expose weaknesses in pathogenic fungi. Lori Huberman, an assistant professor in Cornell's School of Integrative Plant Science, said changing how harmful fungi sense and respond to nutrients could disrupt their growth.
Fungal diseases can account for as much as 20% of staple crop losses before and after harvest, according to the Cornell report. It also said drug-resistant fungal infections in people contribute to a global health burden that can include roughly 3.8 million deaths each year.
Graduate student Brandon Reyes-Chavez and postdoctoral associate Joshua Kerkaert were co-first authors on the study. The National Institutes of Health funded the research.
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