Bioprocess Technology

Research Group | apl. Prof. Dr. Sascha Beutel

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Under supervision of apl. Prof. Dr. Sascha Beutel the research group is conducting fundamental and applied research in the focal area of bioprocess engineering. In our research we are developing complete bioprocesses – from the isolation of genes of interest over the expression in bacterial hosts to the production, isolation and purification of the produced biomolecules. The addressed biomolecules are usually enzymes or otherwise active proteins. The enzymes are intended to be applied in food, aroma or scenting molecule production, e.g. for the production of flavonoids, or sesquiterpenes, wherein processes with isolated enzymes as well as wholecell-catalytical processes are in focus to facilitate cofactor regeneration.

Downstream processing and analytics – methods and technologies

We develop and investigate materials and methods for downstreaming suitable for the produced recombinant enzymes and their respective products. Therefore we are developing new analytical means and methods, as e.g. spectroscopic sensors for online-monitoring of OD, DO, pH in shakeflasks or novel methods for product quantification.

Further works are addressing the invention of new reactor systems as e.g. specific crystallisation reactors or novel photobioreactor concepts, or adapters for the application in disposable reactor systems or dosage modules for shakeflasks to facilitate fed-batch or pH-stat cultures. Furthermore, modern technology concepts as eg. IoT (internet of things), augmented reality or rapid prototyping is in focus of our studies to lift the lab into the 21st century.

Our research works are often carried out in close cooperation with the Scheper group as well as with various partners from academia and industry.

Bioprocess technology

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In bioprocess technology, different aspects of bioprocess development are dealt with. In addition to the control, regulation and optimisation of cultivation processes of bacteria, fungi and mammalian cells, investigations are carried out on enzymatic processes. Some of the laboratories and the pilot plant have SI approval so that work can be carried out with recombinant organisms of this safety level. Currently, organisms for the production of antibiotics, various enzymes, food supplements, cytokines, antibodies and vaccines are being studied in detail. Bioreactors (including single-use systems and ceramic hollow fibre reactors) up to 50 litre scale are available.

Downstream processing

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Downstream processing is one of the cost-driving factors in biotechnological production. The adaptation of new techniques or alternative materials is the focus of work here: Filtration, extraction, chromatography and membrane adsorber processes are available. Industrial processes can be reproduced from laboratory to pilot plant scale. The processing methods are tested, adapted and optimised with regard to their suitability for individual problems. Furthermore, new purification technologies are developed in close cooperation with industry, such as particle-permeable membrane adsorption processes or high-throughput screening processes for the rapid and precise determination of purification parameters.

Bioanalytics

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In the field of bioanalytics, the Beutel working group is dedicated to the development of bioanalytical methods such as the quantification of vitamin B12 in food or the identification of fragrances and flavours from recombinant production. Another focus is the development of sensors and sensor concepts, e.g. for online monitoring of pH, pO2 and OD, for fluorescence measurement of proteins, NADH or similar, or for the use of in situ microscopy in bioprocess monitoring.

Digitalisation

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In the area of digitalisation, the Beutel working group is researching the realisation of interactive digitally supported laboratory infrastructure. In addition to the bidirectional integration of laboratory devices into a LIMS, this includes the entire process development and control on a digital basis as well as interactive collaboration with the digital infrastructure in the form of suitable interaction media, such as SmartGlasses, touch beamers or Smartspeakers.

Research partnerships

Collaborative projects

Research partner

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EFRE-Project: RESI - Innovative Utilization of Residual Materials

This project receives funding from the European Regional Development Fund (EFRE) and the State of Lower Saxony. Within TCI’s subproject, the focus is on the biotechnological production of biopolymers.

The plastics industry is under increasing pressure to develop alternative, more biodegradable materials due to the growing prevalence of microplastics in the environment. The RESI project addresses this challenge by aiming to produce biopolymers such as polyhydroxyalkanoates (PHAs) using microorganisms. To achieve this goal, production processes are first established using natural PHA-producing microorganisms such as Cupriavidus necator, which serve as a benchmark for subsequent recombinant production systems. Recombinant strains based on Escherichia coli (E. coli) are then developed, and their cultivation and production performance are evaluated. In addition to process intensification for optimal production, suitable analytical methods for the quantification of PHAs must also be established. In a further step, various residual materials from agricultural processes are investigated for their suitability as cost-effective medium components in order to improve the economic viability of the process. Particular attention is given to by-products such as molasses, whey, and centrifuge protein as alternative carbon and protein sources.

Project Plan

The project begins with the establishment of a PHA production process based on natural producer strains, complemented by quantitative analytical methods for PHA determination. This process is subsequently scaled up to reactor level and thoroughly investigated as a benchmark process. In parallel, molecular biology work is carried out to engineer recombinant E. coli strains capable of producing PHAs. Once successful production has been demonstrated, these recombinant strains are also scaled up to reactor level, and the process is further optimized and intensified. To enhance the economic efficiency of the production process, various agricultural residual materials are evaluated as medium components, and their optimal proportions for cost-effective production are determined. Finally, the overall process architecture is assessed with regard to its sustainability through a comprehensive life cycle assessment (LCA).

Cooperation

The project is carried out in collaboration with the Institute for Bioplastics and Biocompositions at the University of Applied Sciences and Arts Hannover as well as the companies Vogelsang GmbH & Co. KG and Holzmühle Westerkamp GmbH.

Project Partners:

  • Institute for Bioplastics and Biocomposites, University of Applied Sciences and Arts Hannover, Prof. Dr. Andrea Siebert-Raths, Hannover
  • Vogelsang GmbH & Co. KG, Andreas Fastenau, Essen
  • Holzmühle Westerkamp, Dr. Kolja Ostendorf, Visbek
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EFRE-Project: ISM4MP - In Situ Microscopic Monitoring of Enzymatic Microplastic Degradation

This project receives funding from the European Regional Development Fund (EFRE) under the special call “Strategic Technologies for Europe Platform (STEP)” for innovative collaborative projects in applied research, as well as from the State of Lower Saxony. The project focuses on the monitoring of enzymatic degradation processes of biopolymer microparticles using in situ microscopy.

The plastics industry is facing increasing pressure to develop effective methods for the degradation of plastics due to the continuous accumulation of microplastics in the environment. The ISM4MP project addresses this challenge by aiming to degrade a wide range of polymer microparticles using plastic-degrading enzymes. To achieve this goal, production processes for the recombinant expression of the required enzymes in Escherichia coli (E. coli) are first established. The enzymes are subsequently isolated and purified for use in model degradation experiments. To monitor these degradation processes, a novel analytical technique based on in situ microscopy is being developed. This technology will be capable of documenting the reduction in particle volume of microplastic particles over time. For this purpose, not only must the in situ microscopy system be adapted and optimized for this application, but dedicated image analysis algorithms must also be developed to enable the precise detection and characterization of microplastic particles under flow conditions. In addition, suitable analytical methods for polymer quantification are established to correlate conventional analytical data with the results obtained from in situ microscopy. In a further work package, various polymer microparticles will be investigated and evaluated for their aquatic toxicity by the project partner Noack Laboratorien GmbH. Particular attention will be paid to assessing the relationship between particle size and toxicity.

Project Plan

The project begins with the selection of enzymes capable of degrading representative polymers. The selected target polymers include examples of carbon–carbon (C–C) linked polymers, carbon–heteroatom (C–X) linked polymers, and biopolymers. Subsequently, molecular biology work is carried out to engineer recombinant E. coli strains for enzyme production. Once successful enzyme production has been established, the enzymes are applied in model degradation studies of microplastic particles, while the in situ microscopy system is adapted to monitor and document degradation kinetics. This work includes both the adaptation of the in situ microscopy (ISM) technology for this novel application and the development of image-processing algorithms for the accurate determination of particle sizes under flow conditions. To assess the actual environmental risks associated with microplastic particles, additional aquatic toxicity studies are conducted by the project partner Noack. These investigations aim both to determine acute toxicity and to elucidate the influence of particle size on toxicological effects. For the first time, the project will establish an online measurement technology capable of monitoring inert plastic particles within the critical microplastic size range and tracking their degradation over time.

Cooperation

The project is carried out in cooperation with Noack Laboratorien GmbH.

Project Partner:

  • Noack Laboratorien GmbH, Dr. Christian Maeß 
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Contact

Sascha Beutel Sascha Beutel
apl. Prof. Dr. Sascha Beutel
Address
Callinstraße 3-9
30167 Hannover
Building
Room
167
Sascha Beutel Sascha Beutel
apl. Prof. Dr. Sascha Beutel
Address
Callinstraße 3-9
30167 Hannover
Building
Room
167