Carboxylic acid reductases (CARs) are attractive catalysts for the synthesis of valuable aldehyde building blocks. However, the application of CARs still remains a challenge because CARs depend on essential NAD(P)H and ATP cofactors that need to be regenerated. To overcome this limitation, locally immobilized multi-enzyme constructs will be designed with superior catalytic activity and stability in E. coli compared to unfused enzymes. To this end, catalytic partners will be fused with optimized peptidic linkers using iterative cycles of structural bioinformatics, simulations of diffusion and reaction systems, and experimental in vitro and whole-cell validation. From an applied viewpoint, the project shall provide transferable rational knowledge to guide the integration of CARs into self-sufficient multi-enzyme fusion assemblies. From a basic research viewpoint, the project contributes to elucidating the impact of fusion on the performance of multienzyme fusion assemblies.
Dr. Benoit David
IBG-4 - Bioinformatics
Prof. Dr. Holger Gohlke, PMC - Computational Pharmaceutical Chemistry and Molecular Bioinformatics, HHU Düsseldorf
Dr.-Ing. Eric von Lieres, IBG-1 - Systems Biotechnology, Forschungszentrum Jülich
Prof. Dr. Dörte Rother, IBG-1 - Systems Biotechnology, Forschungszentrum Jülich
Prof. Dr. Svyatoslav Kondrat, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw
Max-Planck-Institut for Intelligent Systems, Stuttgart
Institute for Theoretical Physics, University of Stuttgart, Stuttgart
01.10.2023 - 31.03.2025
CasCar is part of the NRW-Strategieprojekt BioSC and thus funded by the Ministry of Culture and Science of the German State of North Rhine-Westphalia.