The carbohydrate utilization regulator Cbr1 coordinates nutrient-specific gene activation with selective carbon catabolite repression in a basidiomycete yeast
- 1Plant Pathology and Plant-Microbe Biology Section, School of Integrative Plant Science, Cornell University, Ithaca, New York, United States of America
- 2Microbiology Department, Cornell University, Ithaca, New York, United States of America
Abstract
Cells must sense and respond to nutrients to survive. To efficiently grow in mixed carbon environments, microbes repress genes necessary to utilize carbon sources that require substantial resources to catabolize when a simpler carbon source, such as glucose, is present. This process is known as carbon catabolite repression. Canonically, in fungi, nutrient sensing transcriptional networks are composed of carbon source-specific transcription factors that activate carbon source utilization genes and carbon catabolite repression regulators, which broadly repress all nonpreferred carbon source utilization genes when a preferred carbohydrate is present. In contrast to this model, we identified a transcription factor (Cbr1) in the basidiomycete yeast Rhodotorula (Rhodosporidium) toruloides that specifically inhibits glucose-mediated repression of disaccharide and proline utilization, presenting a mechanism of tailored carbon catabolite repression regulation that combats a negative feedback loop formed when glucose is released during disaccharide utilization. Cbr1 is also required for cellobiose, gentiobiose, carboxylic acid, and fucose utilization. Using transcriptomic and molecular analyses, we demonstrated that catabolism of these carbon sources is not metabolically linked, but genes necessary for their utilization are coactivated by Cbr1 in response to each of the carbon sources. This coactivation suggests R. toruloides may encounter these carbon sources together, potentially during complex interactions among microbes in nature. Coregulation of nutrient-specific gene activation and carbon catabolite repression by a transcription factor establishes a previously uncharacterized mechanism for building nutrient sensing transcriptional networks in fungi. Characterizing diverse nutrient sensing regulatory mechanisms is critical for understanding resource acquisition during fungal pathogenesis, where carbon catabolite repression is important for virulence and drug tolerance, and metabolically engineering fungi for green biotechnology.
Fungi must sense and prioritize nutrients to compete with microbes and form relationships with plants and animals. This study shows that the regulator Cbr1 coordinates nutrient use and avoids negative feedback that could block access to some food sources.
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BibTeX
@article{reyeschavez2026carbohydrate,
title = {{The carbohydrate utilization regulator Cbr1 coordinates nutrient-specific gene activation with selective carbon catabolite repression in a basidiomycete yeast}},
author = {Brandon Reyes-Chavez and Joshua D. Kerkaert and Lori B. Huberman},
journal = {PLOS Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pbio.3003983},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003983},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The carbohydrate utilization regulator Cbr1 coordinates nutrient-specific gene activation with selective carbon catabolite repression in a basidiomycete yeast
AU - Brandon Reyes-Chavez
AU - Joshua D. Kerkaert
AU - Lori B. Huberman
PY - 2026
DA - 2026/09/01
JO - PLOS Biology
DO - 10.1371/journal.pbio.3003983
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003983
AB - Cells must sense and respond to nutrients to survive. To efficiently grow in mixed carbon environments, microbes repress genes necessary to utilize carbon sources that require substantial resources to catabolize when a simpler carbon source, such as glucose, is present. This process is known as carbon catabolite repression. Canonically, in fungi, nutrient sensing transcriptional networks are composed of carbon source-specific transcription factors that activate carbon source utilization genes and carbon catabolite repression regulators, which broadly repress all nonpreferred carbon source utilization genes when a preferred carbohydrate is present. In contrast to this model, we identified a transcription factor (Cbr1) in the basidiomycete yeast Rhodotorula (Rhodosporidium) toruloides that specifically inhibits glucose-mediated repression of disaccharide and proline utilization, presenting a mechanism of tailored carbon catabolite repression regulation that combats a negative feedback loop formed when glucose is released during disaccharide utilization. Cbr1 is also required for cellobiose, gentiobiose, carboxylic acid, and fucose utilization. Using transcriptomic and molecular analyses, we demonstrated that catabolism of these carbon sources is not metabolically linked, but genes necessary for their utilization are coactivated by Cbr1 in response to each of the carbon sources. This coactivation suggests R. toruloides may encounter these carbon sources together, potentially during complex interactions among microbes in nature. Coregulation of nutrient-specific gene activation and carbon catabolite repression by a transcription factor establishes a previously uncharacterized mechanism for building nutrient sensing transcriptional networks in fungi. Characterizing diverse nutrient sensing regulatory mechanisms is critical for understanding resource acquisition during fungal pathogenesis, where carbon catabolite repression is important for virulence and drug tolerance, and metabolically engineering fungi for green biotechnology. Fungi must sense and prioritize nutrients to compete with microbes and form relationships with plants and animals. This study shows that the regulator Cbr1 coordinates nutrient use and avoids negative feedback that could block access to some food sources.
SN - 1545-7885
ER -