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BIOINTENSE Report Summary

Project ID: 312148
Funded under: FP7-KBBE
Country: Denmark

Periodic Report Summary 3 - BIOINTENSE (Mastering bioprocess Integration and intensification across scales)

Project Context and Objectives:
BIOINTENSE represents a revolution in bioprocessing and brings together two communities of world class researchers – those involved in biocatalytic processing (using enzymes to fabricate novel compounds of potentially very high value) and those involved in creating miniature microfluidic systems as a novel reactor and product recovery configuration for process development and potentially production). Indeed, microfluidic enzyme reactors represent a powerful tool for optimization and intensification of biocatalytic processes normally preformed at larger industrial scale. The modularity brings unique benefits. Testing of different process strategies is more flexible, faster and cheaper. In order to exemplify and test the concepts a model reaction system has been chosen – the use of transaminase based synthesis of chiral amines. It is of major importance to the pharmaceutical and other high value chemical industries.

Project Results:
The model reaction system has been studied with three separate model systems using a specific substrate and product combination and three alternative amine donors. Each have been chosen to exemplify different strategies to overcome the current process bottlenecks. In this way the versatility of the microfluidic system will be demonstrated. Enzyme and protocols have been established so that initial characterization has been completed setting the boundaries for operation. The microfluidic systems themselves have also been specified, designed and tested. Review of the possibilities of microfluidic technology and biocatalysis, published in Trends in Biotechnology, demonstration system has been established using optimal reaction conditions and integrating product recovery, kinetic profiling on biocatalysts has been established by integration of reaction engineering, microfluidics and chemometrics.

Potential Impact:
The use of microsystems for biocatalysis is still in its infancy and it has been important to introduce the project at 1st and 2nd International Conference on Industrial Transaminase Biocatalysis 2013 (Stockholm, Sweden) and 2015 (Greifswald, Germany) as well as the 2nd and 3rd International Conference on Implementation of Microreactor Technology in Biotechnology – IMTB 2013 (Cavtat, Croatia) and IMTB 2015 (Opatija, Croatia), where the project has taken a major role in organization and presentation. These are important showcases to demonstrate what can be achieved. A further event on IB held in Brussels (2013) also provided a forum to demonstrate the first operation of these microfluidic systems. Ultimately the project has delivered a platform capable of testing new ATA reactions and their biocatalysts in microfluidic modular format. The associated hardware and software including protocols and guidelines for operation have also been forthcoming and are essential in order that industry can take up the concepts. Industrial interest has been considerable with larger companies like DSM and Sigma-Aldrich already committed. Likewise the SMEs involved are also developing new businesses. There has already been interest from outside the consortium and we expect this to develop into new projects beyond BIOINTENSE. At the end of the project we held a 2-day conference in Ghent (Belgium) where guests were invited to hear about the final results of the project (Day 1 open with invited audience and speakers both from inside and outside the consortium; Day 2 closed with a final wrap-up of the project). Some tools and materials for the consortium are already suitable for development into commercial products, including: microfluidic chips and systems for testing biocatalytic processes, sensor technology, new enzymes, new chemicals, immobilized enzymes, screening tools and biocatalyst characterization tools.

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