Science1 publisher3 min readPublished
Cbr1 overrides the glucose signal that would stop a yeast from eating cellobiose
In a yeast that stores up to 70 percent of its biomass as fat, a transcription factor called Cbr1 both switches on the enzyme that splits cellobiose and blocks the glucose signal that would silence that gene.
The Scientist · Science desk
What happened
- A PLOS Biology paper published Sept. 1 names Cbr1, a transcription factor in the single-celled fungus Rhodotorula toruloides, as a regulator of the genes that break complex sugars down into glucose.
- Cbr1 acts in two directions at once, switching on the genes whose enzymes cleave cellobiose and inhibiting the machinery that would otherwise repress those same genes once glucose is present.
- The team measured expression of every gene in the R. toruloides genome, in ordinary cells and in strains it had engineered, and used the comparison to sort out which genes Cbr1 controls.
- The study organism, Rhodotorula toruloides, accumulates up to 70% of its biomass as lipids.
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Why it matters
- capability A single named regulator gives strain engineers one place to intervene when a production yeast stalls on a disaccharide feedstock. Otherwise it is transporters and hydrolases, tuned gene by gene.
- constraint The relief reported here applies to sugars built from two glucose units. The switch has not been shown to unlock the rest of a mixed plant hydrolysate.
- precedent If nutrient-sensing regulators of this kind are conserved in pathogenic fungi, they become a candidate target class. Testing that takes a homolog experiment in a species that causes disease.
Cellobiose is two glucose molecules joined together [3]. Each glucose carries six carbon atoms [14], so a cellobiose molecule the yeast never opens is twelve carbon atoms left in the medium [15]. To open it, the cell has to express an enzyme that cuts the bond. The cut releases free glucose, and free glucose is the signal that tells a fungus to stop expressing genes for carbon sources that cost more energy to use [20]. The glucose the enzyme frees shuts the enzyme's own gene down [4].
"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," said Lori Huberman, an assistant professor in the Plant Pathology and Plant-Microbe Biology Section of the School of Integrative Plant Science [10][16].
The comparison that got them there was whole-genome expression measurement in ordinary cells and in strains the lab had engineered, which is how Cbr1-dependent genes were separated from the rest [7]. Transcriptomics measures RNA abundance. Whether a strain that transcribes more hydrolase actually eats cellobiose faster, or stores more lipid while doing it, is a separate measurement. The release does not include growth or yield figures for the engineered strains.
The paper's title describes "selective carbon catabolite repression" [18], and the selectivity is real: the relief reported covers cellobiose and other complex sugars built from two glucose molecules [6]. Huberman's pitch for the organism is broader than that. "These yeasts that we studied are able to eat all of the breakdown products of the plant cell, so they can be fed grasses grown on marginal lands or agricultural waste," she said [9]. She also said groups are working to route the yeast's lipids into products such as environmentally friendly plastics or biofuel [19].
The announcement sets the stakes with two field-level numbers. Fungal diseases can contribute up to 20% of staple crop losses before and after harvest [12], and phys.org puts deaths linked to rising drug-resistant fungal infections in humans at roughly 3.8 million globally each year [13]. Both are context for why nutrient sensing is studied. Neither is a result of this experiment.
Huberman is blunt about what this means for pathogens. "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," she said [11]. The work itself sits in one basidiomycete yeast valued for its fat content [1][8], with Brandon Reyes-Chavez, a graduate student, and Joshua Kerkaert, a postdoctoral associate, both in Huberman's lab, as co-first authors [17].
What to watch
- Measured consumption and lipid yield for a Cbr1-modified strain grown on cellobiose-rich hydrolysate.
- A deletion or knockdown of a Cbr1 counterpart in a fungus that actually causes plant or human disease.
- Identification of the repressor machinery Cbr1 acts against, which would say how transferable the circuit is between species.