Using Yeats Pheromones for the control of biotechnological processes

• Applicants: Dr. Kai Ostermann; Professor Dr.-Ing. Thomas Walther, since 9/2018
• Subject Area: Biological Process Engineering
• Term: from 2015 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 275640797

Since the implementation of industrial production process in the biotech industries in the 1940s these processes are dominated by the application of monoseptic cultures. This allows the defined and controlled conversion of substrates by the specific microorganism. However, this is associated with the limitation of the conversions to the metabolic capabilities of this organism. Combining the metabolic capabilities of differently functionalized cells of on species or of cells from different species will significantly enhance the variability of conversions in one process. Up to now the composition and the metabolic activities of mixed cultures were hard to control in a bioreactor. This challenge is addressed in the proposed project. In previous work of the submitters it was shown that using adequately engineered cells the application of pheromone based cell-cell communication in yeasts is suitable for controlled signal amplification and modulation. Furthermore such cells were used for the design of biological whole-cell based sensor-actor-systems .Interestingly these systems can not only be used for communication intra-species but for inter-species communication either. This approach of synthetic biology using the pheromone system of yeast for the application in intra- and inter-species communication between yeast will be applied to establish the control of compositions of consortia in biotechnological processes. By the generation of specifically engineered yeast this concept will be advanced considerably. Intra- and inter-species communication should be applied to control subpopulations in a bioreactor, i.e. subpopulations of different yeasts are being controlled in a specific manner. Different functionalized cells are activated and deactivated in defined temporal sequences. This means that the specific expression or repression of one gene causing the functionalization of the cell is controlled. This way specific metabolic capabilities / protein expressions will be activated in sequence or parallel to demonstrate the applicability of the intra- and inter-species communication in biotechnological processes. The achieved data will be used to develop mechanistical models that describe the dynamics of the populations allowing the development of strategies for multi stage process design. This approach requires a considerable expansion of the modules of existing yeast strains. Notably yeasts that allow a controlled modulation of growth are being developed. Besides the established inter-species communication between S. pombe and S. cerevisiae in the context of this project it should be investigated whether the biotechnological relevant yeast P. pastoris can be controlled by pheromone based communication either.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Thomas Bley, until 9/2018