Scientists have taken a step toward a better understanding of how fungi sense and respond to nutrients in the environment, which is critical for engineering fungi for green technologies and for combatting fungal pathogens and their resistance to treatments.  

Fungal diseases can contribute up to 20% of staple crop losses before and after the harvest, and rising drug-resistant fungal infections in humans can lead to roughly 3.8 million deaths, globally per year. 

A new study, published Sept. 1 in PLOS Biology, identified a transcription factor – proteins that turn genes on and off and regulate what genes are going to be expressed – called Cbr1 in a yeast, which is a single-celled fungus, called Rhodotorula toruloides. Cbr1 is responsible for regulating genes involved in breaking down complex sugars into glucose, so the carbon is more accessible for use as food by both activating the genes’ expression and  bypassing a negative feedback loop that would otherwise repress genes that facilitate utilizing complex sugars.  

Unraveling how fungi sense nutrients helps scientists gain insight into environmental nutrient cycling, as fungi are key decomposers that return nutrients from plant biomass to the soil. It also helps identify important targets for treating diseases from pathogenic fungi.  

“The fungus in this paper is not a serious pathogen, but many fungi are, for either plants or animals. We know that if we modulate their ability to sense and respond to nutrients, we can disrupt them,” said Lori Huberman, assistant professor in the Plant Pathology and Plant-Microbe Biology Section in the School of Integrative Plant Science (SIPS) in the College of Agriculture and Life Sciences. Co-first authors include Brandon Reyes-Chavez, a graduate student, and Joshua Kerkaert, a postdoctoral associate, both in Huberman’s lab.  

R. toruloides also has potential as a replacement for petroleum, as it accumulates up to 70% of its biomass as lipids (fats). People are currently working to metabolically engineer the organisms to take those lipids and direct them toward making other molecules that are useful, Huberman said, such as for making environmentally friendly plastics or biofuel. 

“These yeasts that we studied are able to eat all of the breakdown products of the plant cell, so they can be fed on grasses grown on marginal lands or agricultural waste,” Huberman said. “We can give them waste and they can utilize that.”  

R. toruloides feeds on carbon found in plant tissue, and the most accessible form of that carbon is glucose, with each molecule containing six carbon atoms. “Fungi always want to eat the best mix of sugars for them,” Huberman said. “The thing they most like to eat is glucose, so if there is glucose around, the fungi are going to repress the expression of genes that are necessary to utilize carbon sources that require more energy.”  

In the study, the team used a technique called transcriptomics, which allowed them to measure the gene expression of all the genes in R. toruloides’ genome, and in the genomes of strains of R. toruloides that the researchers had engineered. The techniques allowed them to identify genes regulated by Cbr1.  

One of those genes expresses an enzyme that breaks down a plant sugar called cellobiose, which is made up of two molecules of glucose, the most desirable food source for fungi. But in the presence of that glucose, and in order to prioritize it over other carbon sources that require more energy to break down, the fungi represses genes that utilize cellobiose, which then restricts access to the glucose cellobiose contains, creating a negative feedback loop. The researchers found that Cbr1 not only cleaves cellobiose apart, but also inhibits the mechanism that would normally repress the genes to utilize cellobiose.  

“It breaks that negative feedback loop and allows the cell to keep seeing those carbon sources that are around, even though they are being broken down into glucose,” Huberman said.  

Cbr1 also breaks this negative feedback loop for other complex sugars made up of two glucose molecules. Understanding these mechanisms is critical for future metabolic engineering for green biotechnology and controlling fungal infections. 

The study was funded by the National Institutes of Health.