The manufacturing process of biological products is complex and requires the use of living cells. Great progress has been made with industrial production techniques but contaminations are still a considerable problem the industry faces. Insufficient control of contaminations in bioreactors could compromise entire batches, resulting in high expenses. A contamination could lead to facilities or equipment having to be shut down for lengthy periods of time in order to conduct investigations and sterilize reactors. Ensuring that the bioreactors only contain the desired producing organism is critical to facility productivity, bioreactor throughput and product quality.
We, Team Chalmers Gothenburg, have developed a novel strategy to detect and combat contaminations in continuous bioreactors, using Saccharomyces cerevisiae as the producing organism.
The method for detection utilizes the pheromone pathway in S. cerevisiae where the GPC-receptor (Ste2) has been replaced with a fusion receptor, allowing the cells to detect ligands from contaminants. When a ligand binds to the fusion receptor it will activate a phosphorylation cascade within the cell, inducing an expression of red fluorescent proteins that can be observed externally. The method for combating the detected contaminant is based on the use of UV-radiation, which effectively harms all living organisms. In order to prevent the producing cells from becoming inviable from the irradiation treatment, a DNA-repair system from the bacterium Deinococcus radiodurans is implemented into the cells. D. radiodurans is renowned for its extreme resistance to radiation, and our theory is that implementing these enzymes may increase S. cerevisiae's resistance to radiation, allowing it to survive while the contaminant dies.