Continuous Process of Protein Crystallization

The CONCRYS project is an international collaboration that combining expertise in chemical engineering (Rzeszw University of Technology), biotechnology (BOKU University of Vienna) and mathematical modelling (Otto-von-Guericke University Magdeburg). The aim is to revolutionize the production and purification of high-quality bioactive proteins, which are essential compounds for applications such as biomedical diagnostics and disease treatment. They can also be used as food supplements or as a substitute for animal-based foods. Protein crystallization is a complex process and batch production methods are used which are costly due to their limited efficiency. We will develop and implement a continuous crystallization process. In this process, water is evaporated from the protein solution using a stream of hot air, which continuously maintains the conditions necessary for crystallization. A continuous process offers advantages over conventional batch production, such as lower requirements for protein stability, higher yields and significantly higher production throughput. Another goal is to develop a mathematical model of continuous crystallization to understand and control the various factors that influence protein crystallization. Continuous protein crystallization also requires continuous synthesis of the desired protein. One of the major challenges is the genetic instability of cell systems used for protein synthesis. The aim is to achieve spatial separation of E. coli cell growth and protein production in a continuous two-step process. Importantly, this production cell line also allows the protein to be secreted into the cell supernatant, so that cultivation and crystallization can be directly coupled after cell separation. Another goal is to produce several proteins simultaneously in one process using mixed cultures. In this case, proteins with a helper function can be provided directly in the process and, for example, the processability of the cell broth can be improved or several different proteins can be produced in precisely the desired quantitative ratios. We will study population dynamics, i.e. how the different cell populations develop in the long term and how this behavior can be specifically influenced. The CONCRYS project will build the knowledge base to make the production of high-quality proteins more efficient and sustainable. This will improve global access to essential proteins, make them cheaper and have a profound impact on several industries.