CARBAZYMES

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was formed. The consortium now brings together capabilities enabling not only the discovery of suitable natural enzyme starting points, but their immediate engineering into demonstrated effective industrial biocatalysts for highly desirable aldol reactions tolerant to low-functionalised substrates.”

Enzyme catalysis The CarbaZymes project is responding to the heightened level of industrial demand by investigating the use of biocatalytic synthesis as a basis for the development of widely needed chemicals and active pharmaceutical ingredients. In this work researchers are drawing inspiration from the natural world, aiming to develop robust enzymes for C–C bond forming reactions. “We work with an SME that has a lot of expertise in utilising meta-genomic information. They have

for a polymer material, for chemicals that are utilised in bulk quantities across the world,” says Professor Fessner. “It’s clearly very important to establish more sustainable pathways to make such monomer materials as soon as we can. Even preventing a small fraction of pollution stemming from their production would still have a huge impact, as an enormous amount of these materials are produced chemically every year.” The wider, longer-term goal is to utilise sustainable resources as starting materials for next-generation synthetic biological processes, reducing our dependence on fossil fuels, which in the long run will help protect the environment and boost the competitiveness of European industry. While this is very much a long-term goal, Professor Fessner says that important progress has already been made in the course of the project. “Alongside

We aim to build on existing knowledge, to develop a platform with many robust enzymes and variants that could be applied for different purposes, under different conditions and for different new reactions useful in industry the capability to produce a large variety of enzymes via gene synthesis,” explains Professor Fessner. A second element of the project’s work centres around utilising and modifying known enzymes. “We aim to broaden their catalytic capabilities. This means broadening their substrate scope and broadening their window of tolerance for high concentrations of substrates, to achieve high concentrations of products that can be more easily isolated,” outlines Professor Fessner. “We are developing reactions that are likely not found anywhere in nature. These reactions are highly relevant as a more sustainable approach to major industrial processes.” Many of the enzymes commonly found in nature can in principle be applied in carboligation reactions, yet only a few have been investigated to a level where they can be utilised for industrial processes. Widening the knowledge base on these enzymes will bring them significantly closer to - or even into - practical application. “We aim to build on existing knowledge, to develop a platform with many robust enzymes and variants that could be applied for different purposes, under different conditions and for different new reactions useful in industry,” says Professor Fessner. This research is designed to respond effectively to market needs, and help boost the competitiveness of the European chemical and pharmaceutical industries. “For example, we are looking at monomers

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identifying suitable enzymes we’ve also been working to develop them to a stage where they can be directly applied in industrial settings,” he outlines. So far two patents have been filed, and now researchers are looking towards assessing the effectiveness of the reactions that have been developed. “We intend to scale-up those reactions that we have developed at lab scale, to the pilot level and maybe even larger scales. We will test the validity of our approach, and the suitability of these enzymes under applied conditions,” outlines Professor Fessner. “This work will be done in leading industrial labs. Ultimately, we hope CarbaZymes will represent a major stepping stone in paving the way towards a greener future!”

CARBAZYMES Sustainable industrial processes based on a C-C bond-forming enzyme platform Project Objectives

C-C bond forming reactions are at the heart of industrial organic synthesis, but remain largely unexplored due to the lack of broad biocatalytic reaction platforms. CARBAZYMES addresses this challenge by promoting innovation in the field of biocatalytic C-C bond formation at large scale, to strengthen the global competitiveness of the European chemical and pharmaceutical industry. Sustainable processes resulting from this research will have an environmental impact by replacing energy and resource intensive traditional processes.

Project Funding

Funded by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No 635595

Project Partners

Coordinator

Contact Details

Professor Wolf-Dieter Fessner, Ph.D TU Darmstadt Dept of Organic Chemistry & Biochemistry Alarich-Weiss-Str. 4 D-64287 Darmstadt Germany T: +49 6151 16-23640 F: +49 6151 16-23645 E: fessner@tu-darmstadt.de W: http://carbazymes.com https://www.youtube.com/watch?v=iNlfyDa093g &list=PLvpwIjZTs-LjYqeOiYYqRWlegdihyjGgu

Wolf-Dieter Fessner, Ph.D

Wolf-Dieter Fessner obtained his Ph.D in 1986 and worked as a postdoctoral fellow with George Whitesides (Harvard University) and George Olah (USC, L.A.). Before assuming the chair in Organic Chemistry at the Technische Universität Darmstadt in 1998, he was professor at RWTH Aachen. His research interests are in the area of biocatalysis for applications in organic synthesis, with particular emphasis on the discovery and development of novel enzymes for stereoselective carbon-carbon bond forming reactions and the synthesis of complex oligosaccharides.

Analysis of structure-function principles of complex aldolase structures.

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