Liquid-phase design to enhance enzyme stability and productivity

• Applicants: Privatdozent Dr.-Ing. Christoph Brandenbusch; Professorin Dr.-Ing. Katrin Rosenthal
• Subject Area: Biological Process Engineering
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 555504947

Despite the potential of biocatalysis in promoting a sustainable bio-economy, optimal liquid phase design for enzymatic reactions remains a challenge due to its complexity and the sensitivity of enzymes to environmental factors like solvent types, concentrations, and reaction conditions. The proposed project aims to systematically explore and improve the reaction conditions to maximize both the catalytic activity and stability of enzymes, specifically the enzyme cyclic GMP-AMP synthase. This enzyme, important in the synthesis of cyclic dinucleotides, shows promise for pharmaceutical applications but is hindered by its low stability under typical reaction conditions. By investigating the interactions of various co-solvents and excipients with the enzyme, the project seeks to develop methodologies that can prevent enzyme deactivation and precipitation, enhancing both enzyme solubility and stability. The research will employ a multidisciplinary approach combining experimental and theoretical methods to establish a comprehensive understanding of the liquid-phase environments that best support enzymatic activity and stability. This will involve detailed thermodynamic analysis and the development of new biocatalytic models to predict and optimize reaction conditions. Ultimately, the project aims to establish a set of best practices for enzyme stabilization that can be generalized to other enzymes and biocatalytic applications, thereby advancing the field of biotechnology and offering potential economic and environmental benefits.

• DFG Programme: Research Grants