Macro-scale engineering
Our bioprocess engineering efforts include the engineering of suitable enzymes and production strains for small molecule and protein production, the establishment of tailored laboratory-scale bioreactor cultivation protocols, and the development of intensified processing schemes such as separation-integrated bioprocesses in which products are removed in situ to relieve inhibitions or maintain thermodynamic driving forces in enzyme reactions. These aspects emphasize the strong application-oriented focus of our group and the goal to ultimately put our academic efforts into an economically or otherwise societally relevant context.
To this end, our group has recently developed a metabolically engineered strain of the bacterium Escherichia coli which no longer requires the vitamin biotin for growth. This biotin-independent strain can be used to efficiently produce otherwise toxic and therefore difficult to produce biotin-binders, such as the high-value protein streptavidin, which is a versatile tool used in various biotechnological applications. In addition to these strain-engineering efforts, we have developed a three-stage bioreactor process in liter-scale with optimized growth and production phases enabling streptavidin production at hitherto unmatched titers and volumetric productivities.
References
Jeschek, M., et al.: Biotin-independent strains of Escherichia coli for enhanced streptavidin production, Metabolic Engineering, 2017, external pageDOI.
Since downstream processing is a major contributor to the costs of biotechnological products, we have been very active in developing process-integrated purification technologies for the retrieval of highly pure compounds such as rare sugars. More precisely, we conceived a simulated-moving bed (SMB) unit which allows to continuously isolate optically pure d-psicose enzymatically produced from low-cost sucrose with very high efficiency and yield directly from the production broth. This in situ product removal is essential to overcome thermodynamic limitations of the enzymatic sugar isomerization and to achieve full conversion of the starting material to the desired product. In this context, we have also carried out a multi-objective optimization study to analyze the economic viability of the developed rare sugar production pipeline.
Current projects related to bioprocess engineering in our group include the establishment of a biosensor-based platform for the production of biofuels in Pseudomonas putida as well as the development of a continuous method for the low-cost purification of streptavidin.
References
Wagner, N., et al.: A Separation‐Integrated Cascade Reaction to Overcome Thermodynamic Limitations in Rare‐Sugar Synthesis, Angewandte Chemie, 2015, external pageDOI.
Wagner, N., et al.: Multi-objective optimization for the economic production of d-psicose using simulated moving bed chromatography, Journal of Chromatography A, 2015, external pageDOI.