Design and Assembly of a Multi-enzyme CO2 Fixation System

• Applicant: Professor Ulrich Schwaneberg, Ph.D.
• Subject Area: Biological Process Engineering ; Biochemistry ; Bioinformatics and Theoretical Biology ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 410477515

The use of fossil fuels not only leads to a shortage of resources and energy but also to environmental problems such as smog and greenhouse gases. The use of renewable resources such as solar energy and biomass to produce energy and chemicals has become an important direction for sustainable development. The third generation of biotechnology based on CO2 is one of the hot spots in biotechnology research at present. In the latter respect, the advantage of enzymatic CO2 conversion is that there are no byproducts and the processes are simple and easily tunable. At present, however, the main problems of CO2 conversion are the lack of efficient reduction systems and inefficient cofactor regeneration systems to debottleneck the cascades. The FixZyme project aims to construct a simple, yet effective enzyme cascade for CO2 fixation, which employs a four-step process to stepwise reduce CO2 to yield dihydroxyacetone, a promising industrial precursor. For efficient cofactor regeneration, both enzymatic (an oxygen-tolerant [NiFe]-hydrogenase using H2 to reduce NAD) and photocatalytic/electrochemical approaches will be evaluated. Innovative enzyme fusion and co-immobilization methods will be employed to construct the multi-enzyme cascade. Individual oxidoreductases will be tailored towards optimized catalytic efficiencies and stabilities by using protein engineering. Guided by comprehensive computationally assisted model building and simulations, a fundamental understanding of structure-function relationships, metabolite fluxes, and morphologies will be gained, which further builds the foundation of iterative process and protein engineering trials. To achieve the goal of a highly active and efficient CO2-fixation system, the German and Chinese partners will join their expertises in protein engineering, enzyme production and purification, genetic engineering, computational biology, immobilization and physicochemical analysis. The FixZyme project is of great significance not only for the rational design of highly efficient biocatalysts but also for understanding surface interactions that govern self-assembly and their underlying evolutionary principles.

• DFG Programme: Research Grants
• International Connection: China
• Partner Organisation: National Natural Science Foundation of China
• Cooperation Partner: Professor Dr. Tan Tianwei