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Within the interdisciplinary team, here at Fraunhofer ISC we have developed hybrid catalyst particles. These hybrid catalyst particles consist of photocatalytic building blocks and carrier particles, on which enzymes have been immobilized, presenting the biocatalytic building block.

In the figure one example of a hybrid catalyst particle under a scanning electron microscope view is shown elucidating the principle of a photo-assisted biocatalysis cascade reaction: Photocatalytic building blocks have been intimately mixed via spray-drying technique with biocatalytic building blocks. The biocatalytic building block is carrying commercially available horse-radish peroxidase (HRP) on its surface. The hybrid catalyst particles are suspended in a water-based buffer solution and UV light is turned on. During this photocatalytic step, hydrogen peroxide is formed, which is then used in the biocatalytic step. A model reaction for the activity of horse radish peroxidase is the oxidation of tetramethylbenzidine, shortly TMB. This reaction is proceeding and can be monitored in a blue coloration of the reaction mixture.    

One of the core competencies of the Fraunhofer ISC's particle technology group is the wet-chemical synthesis of tailor-made nano- and microparticles, their modification, characterization and synthesis upscaling to pilot scale. Next to silicon dioxide nanoparticles acting as excellent carrier particles for enzymes, research focuses on photocatalyst materials, e. g. titanium dioxide or carbon nitride particles. 

With our spray-drying technique, the type and amount of building blocks can easily be varied and mixed to hybrid catalyst particles depending on the desired cascade reaction. The hybrid catalyst particles have already been used in flow-reactors of Fraunhofer IMM for the demonstration of industry-relevant, continuous cascade reactions. In flow reactors the hybrid catalyst particles have been heterogeneously distributed and can easily be separated after their use. Further on by using our selective spray-coating technique at Fraunhofer ISC, hybrid catalyst particles have been immobilized directly into microchannels of metal or polymer substrates, which can easily be replaced after their use in a flow reactor. During the cooperation, Fraunhofer IME provided custom-synthesized enzymes for the industry-relevant biocatalytic step. Thus, a modular system for the realization of cascade reactions in flow mode is waiting for you.

In which cascade reaction are you interested? Fraunhofer ISC´s particle technology group will support you in finding and synthesizing suitable particle-based materials or upscaling your particle synthesis or particles´ modification.   

In the Cascade Reaction Project, we established selective fluorination under biologically compatible conditions for the first time and transferred it to a flow process. This approach now gives us access to the biocatalysis toolbox, enabling us to carry out enzyme-catalyzed stereoselective synthesis of fluor alcohols in a further step. The Cascade Reaction Project enabled the use of heterogeneous hybrid catalysts in flow reactors, including the integration of online NMR analysis for process development and monitoring.

In a further work package, the safety-critical production of oxidation equivalents, e.g. hydrogen peroxide, was made possible via a photocatalytic step. The in-situ oxidation of classic reactants, e.g. toluene to benzaldehyde or ethylbenzene to acetophenone, was then coupled to a stereoselective conversion with immobilized enzymes to chiral alcohols or addition products such as mandelonitrile.

In summary, it can be said that the Cascade Reaction Project has enabled the development of a modular synthesis platform for photochemically assisted biocatalysis as an extremely versatile example of cascade reactions. In addition to the development of hybrid catalysts from photocatalysts and enzymes on polymer carriers and supramolecular particles, new concepts for flow reactors and process modules for synthesis and analysis have been developed. These process modules are available to the consortium and interested customers from industry for joint research and development projects.

The Fraunhofer IGB has developed new technologies for immobilizing catalysts on polymer films. These films can be used in transparent flow reactors and easily replaced (see Picture). Through innovative surface functionalizations and immobilization strategies, we can effectively bind both organic and inorganic photocatalysts as well as biocatalysts to structured polymer substrates.

A central element of the technologies applied is the Plasma-Enhanced Chemical Vapor Deposition (PECVD) coating process: It provides covalently attached thin layers with specific functional groups, such as amino, carboxyl, and aldehyde functions. These functional groups are then used to bind the catalysts. The technology is highly scalable, thanks to roll-to-roll coating processes.

For coupling the catalysts from our project partners on the polymer substrate, we have developed various strategies and protocols, ranging from click reactions and coupling reactions of amines and carboxylic acids with carbodiimides to the binding of His-tag enzymes to Zn/NTA-modified films.

The structured films coated with catalysts can be used in falling film microreactors designed by Fraunhofer IMM. The structuring is carried out using hot stamping processes and is customizable.

Would you like to immobilize catalysts? We are happy to assist you in selecting and modifying substrate materials and tailored binding strategies.

Fraunhofer IME delivers scalable, high-performance, biocatalysts tailored for sustainable fine chemical synthesis through enzymatic cascade reactions. By aligning biocatalyst design with process requirements and industry standards, IME's comprehensive approach covers the full development pipeline, from enzyme selection and engineering to scalable production, purification and characterization of catalytic properties (Figure IME).   

Leveraging advanced technology platforms for upstream processing including bacterial and cell-free expression platforms, IME’s scientists achieve scalable downstream production of a diversified biocatalysts portfolio. This provides the flexibility required to support unique production needs ranging from small scale to pilot scale production campaigns.

Our optimized protocols for enzyme immobilization on functionalized carrier such as polymeric films or silica-based nanoparticles, create novel hybrid catalysts which can be efficiently reused and show improved enzyme stability and performance. Tailored enzymatic assays can be developed to evaluate both soluble and immobilized enzyme formats under process-relevant conditions.  

Looking to advance your cascade chemistry with efficient, reliable enzymatic solutions? Collaborate with Fraunhofer IME to integrate tailor-made biocatalysts into your processes, improving catalytic efficiency, boosting sustainability, and reducing production costs in synthesis of fine chemicals.