Saccharomyces cerevisiae, commonly known as yeast, is a biological workhorse. It has been used by humans for thousands of years to brew beer, make wine, leaven bread, and, more recently, to produce large amounts of proteins for therapeutic uses and enzymes for industrial applications.
While yeast is often the organism of choice for making large amounts of a protein of interest, there can be problems when protein production is scaled. The unfolded protein response, or UPR, is one of these issues. When yeast cells try to fold large numbers of proteins, their cellular machinery can become overworked, triggering the UPR. Hundreds of genes are turned on rapidly in an effort to decrease the amount of unfolded protein. A fine line needs to be maintained between making enough protein and not triggering a large UPR, which typically results in decreased yields.
In a recently published study in ACS Synthetic Biology, researchers developed a sensor to monitor the UPR in real time. They engineered a fluorescent protein that turns on when the UPR is activated. They then characterized this sensor in cells with proteins produced at different levels and with configurations known to elicit the UPR. They found that the UPR is caused by both how challenging a protein is for the yeast cells to fold, and how much of it is being produced.
Triggering of the UPR is a limitation in protein production that many industries rely on. Development of this sensor gives a real-time readout that could be useful for scientists and engineers trying to maintain the line between maximal protein production and the health of the yeast cells producing them.