Indisciplinary Research: the Center for Microbial Biotechnology (ZMB) at the Forschungszentrum Jülich

Bioprocess development at IBT-2

At the Center for Microbial Biotechnology (ZMB), four closely collaborating institutes join their forces to advance industrial (or white) biotechnology.

The four are the Institutes of Biotechnology 1 (IBT-1) and 2 (IBT-2) of the Forschungszentrum Jülich GmbH and the Institutes for Molecular Enzyme Technology (IMET) and Bioorganic Chemistry (IBOC) of the Heinrich-Heine-University Düsseldorf. They stand side-by-side on the campus of the Forschungszentrum Jülich, and this proximity contributes greatly to effective teamwork

The ZMB is focused on the development and improvement of production processes for pharmaceuticals, for fine and bulk chemicals and for proteins based on biocatalysis with intact microbial cells or isolated enzymes. It is one of Germany's largest research facilities in this field, comprising more than 150 scientists and PhD or master students, state of the art lab equipment and a...

Photobiotechnology at IMET

The Institute of Biotechnology 1 (IBT-1) is focused on molecular and applied microbiology. One major goal is the development of microorganisms as biocatalysts for the production of industrially or pharmaceutically relevant products from renewable carbon sources, such as amino acids, organic acids, or proteins. Several production strains currently in use by industry were generated at IBT-1, for example, for L-serine or L-isoleucine. A number of ground-breaking discoveries have been made at the institute, including the identification of the first amino acid exporter, LysE.

The metabolic engineering approach requires a global and quantitative knowledge of metabolism and its regulation. Therefore, basic research at the institute is focused on a systems biological understanding of select microbial species such as Corynebacterium glutamicum, Gluconobacter oxydans and Escherichia coli to serve as multipurpose production platforms. Genome-based bioanalytic approaches — DNA microarrays, proteomics and metabolomics — are being extensively used and a close partnership with IBT-2 and its competencies in metabolomics and modeling is fostered. The knowledge gained from "multi-omics" methods meets the challenge of creating the best possible producer strains by optimizing the entire microbial cell ("whole cell engineering").

Photoreactor at IBOC

One fascinating aspect of current work is the establishment of heterologous and artificial metabolic pathways ("synthetic biology") using enzymes from heterologous hosts or enzymes with novel functionalities created by directed evolution. This work incorporates expertises from IMET and IBOC.

The team of IBT-1 currently comprises 50 people headed by Prof. Dr. Michael Bott (m.bott@ fz-juelich.de), a microbiologist with 80 articles and several patents to his name. He is coordinator or member of several national or international research consortia and is an editor of FEMS Microbiology Reviews.

Quantitative biology, the precise and reliable measurement of intracellular processes, is an important tool in bioprocess development. The Institute of Biotechnology 2 (IBT-2) is developing quantitative methods for detailed characterization of the complex biochemical networks inside living cells, with tools for metabolome, fluxome, enzyme and proteome measurements being established. This data is used to build predictive mathematical models that can be applied to the systematic improvement of industrial processes.

A cycle of experimentation, data evaluation, modelling, and experimental design is the driving force of knowledge generation in IBT-2. The institute hosts high performance measurement equipment combined with automated laboratory procedures and lab robotics; it also houses extensive fermentation facilities, ranging from mini reactors up to a pilot plant bioreactor.

In the modelling group the raw data is preprocessed by specially developed algorithms and incorporated in mathematical models using the local supercomputers. Working in close cooperation with IBT-1, researchers at IBT-2 are initiating single cell investigations aiming at the quantitative characterization of genetic processes. These studies are supported on the molecular scale by the design, characterization, and application of functional proteins, work made possible by strong links to IMET and IBOC.

DNA microarray analysis at IBT-1

IBT-2 has a 40-people team lead by the recently appointed Prof. Dr. Wolfgang Wiechert (w.wiechert@fz-juelich.de). His strong background in simulation science and systems biology is recognized in more than 60 journal publications and was honoured by the DECHEMA research prize in 2008.

The Institute of Molecular Enzyme Technology (IMET) of the Heinrich-Heine-University Düsseldorf currently employs 60 staff in five different groups. These cover "biodiversity","microbial expression systems", "photobiotechnology","biotr ansformation", and "applied enzyme technology". They enjoy state-of-the-art instrumentation for molecular biological, biochemical, and highthroughput screening, including a colony-picking robot and a liquid-handling-robot with integrated multifunctional microtiter plate photometer, magnetic separator and vacuum station.

IMET holds a leading position nationally and internationally in the study of bacterial enzymes, both in terms of basic research and biotechnological applications. Novel enzyme genes are identified by metagenomic approaches, and the expression, folding, and secretion of these enzymes are studied. Prof. Dr. Karl-Erich Jaeger (karl-erich. jaeger@fz-juelich.de) is director of IMET. He has published more than 100 research articles and has filed several patents; he is a member of many national and international research consortia, and he is an editorial board member of Applied and Environmental Microbiology and Microbial Biotechnology. Professor Jaeger coordinates the research platform "Protein Expression and Optimization" (ExpressO), financed by the Federal State of North-Rhine Westphalia; and serves as vice-president of the Cluster of Industrial Biotechnology CLIB2021, a consortium of 62 universities, research institutions, investors and large and medium-sized Biotech companies.

The Institute of Bioorganic Chemistry (IBOC) is a recently founded collaboration between Heinrich- Heine-University Düsseldorf and the Forschungszentrum Jülich. Thirty members of staff are currently employed under director Prof. Dr. Jörg Pietruszka (j.pietruszka@fz-juelich.de), who has worked for 15 years in the field of organic synthesis and has about 60 scientific publications. He is a member of several coordinated research projects including ‘ExpressO' (a joint venture with IBT 1+2 and IMET), and he coordinates the Düsseldorf pillar of the ‘graduate cluster for industrial biotechnology'.

The institute has a focus on the development of new synthetic methods and their application in active agents syntheses, with a particular emphasis on the total synthesis of marine natural products. Target molecules include anticancer compounds and derivatives for treating chronic diseases. An increasing number of enzymatic transformations are being used to generate key-building blocks, as was recently demonstrated in the syntheses of a number of marine oxylipins. In addition, renewable sources such as carbohydrates are providing an excellent basis for complex starting materials. Enzyme assays for activity and selectivity screening are developed. The institute just moved into a new building (2006) with a complete state-of-the-art laboratory as well as the corresponding analytical equipment for chemical synthesis as well as for biotechnological investigations.



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