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Australasian Biotechnology (backfiles)
AusBiotech
ISSN: 1036-7128
Vol. 8, Num. 3, 1998
Australasian Biotechnology,
Volume 8 Number 3, May/June 1998, pp. 168-171

Kluyver Institute for Biotechnology in The Netherlands - Unity in Biochemistry

J.L. den Hollander, J.J. Beun, P.L.A. Overbeeke, J. Schalk,

Kluyver Institute for Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands

Code Number:AU98026
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      Text: 14K
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From July 5th until July 24th 1998, a delegation of professors, lecturers, Post-docs and PhD students (20 persons in total) of the Kluyver Institute for Biotechnology in The Netherlands will undertake a study tour to Australia. In this period a number of research institutes, universities and companies in the field of biotechnology and chemical engineering will be visited. Since the Kluyver Institute for Biotechnology is a representative of the European vision on modern biotechnology a comprehensive overview of the institute is presented.


The Kluyver Institute for Biotechnology

In 1895, the microbiologist Beijerinck accepted a chair in general and applied microbiology at the Department of Chemical Process engineering at what was then called the Polytechnical School, Delft. He was one of the first microbiologists to study the role of microorganisms in their micro-environment. He emphasized that microorganisms displayed physiological changes in response to changes in environmental conditions. Knowledge of these interaction processes was used to rationalize the use of microorganisms for production and remediation processes in industry. In 1921, Professor Kluyver succeeded Professor Beijerinck. Trained as a chemical engineer, he became a world-famous microbiologist, introducing the scientific concept of "Unity in Biochemistry" which states that the metabolism in all living creatures (ranging from microorganisms to higher organisms) is based on the same principles. This concept is now widely accepted and is still the basis of the research and education at the Kluyver Institute for Biotechnology (KIB).

    Figure 1. The Kluyver Institute for Biotechnology

Organization

The biotechnological research and education of the Faculty of Applied Sciences (which includes Departments of Chemical Engineering, Materials Sciences, Biochemical Engineering and Applied Physics) at the Delft University of Technology is constituted in the Kluyver Institute for Biotechnology. Approximately 200 people are employed by the institute. The entire process of building block to product (from molecule to process) is the basis for biotechnological research and education in the Kluyver Institute. The subfaculties within the KIB that cover the various research topics are listed in Table 1. The chairs of these sections are shown as well. As can be seen, intensive exchange of scientific knowledge between the subfaculties is established.

Table 1: Research in the Kluyver Institute for Biotechnology

Research Topic Chairs
Microbiology Kuenen, Hooykaas
Biocatalysis and enzymology Heijnen, Duine, Sheldon
Environmental technology Kuenen, Heijnen
Bioprocess design Luyben, Heijnen, Van der Wielen, Van Dedem, Sheldon
Analytical Biotechnology Van Declem, Luyben
Downstream processing Van der Wielen

Yeast research

Within the group of yeast research (microbiology), the (molecular) physiology of industrial relevant yeasts and filamentous fungi, with emphasis on the control of metabolic fluxes, redox metabolism and mixed substrate utilization, is studied. The research is aimed at linking molecular genetic information of industrial yeasts with the performance of the intact organisms under conditions relevant to industrial production processes. Experimental and theoretical (computer) models are being matched.

The microbiological factory

A microorganism can be seen as a small integrated chemical factory. The efficiency in terms of produc tivity, recycling of materials, energy conservation and minimization of waste streams is excellent. Renewable source streams (like water, glucose, ammonia and oxygen) are converted into high quality products (antibiotics, amino acids, food additives, alcohols, esters, polymers etc.). This concept of integration of source streams, energy conservation and minimization of waste streams stimulates research groups at the KIB in elucidating the control mechanisms, coupling of reactions and material recycling mechanisms of the cell. Both internal (genetic engineering) and external process conditions are studied. This research can only be successful if the above mentioned research groups cooperate and contribute to insight of the mechanisms with their own specialism.

Biocatalysis and Enzymology

Within the biocatalysis group fundamental and applied research on the application of enzymes as (enantioselective) catalysts for the production of fine chemicals is being carried out. Optimal process conditions such as solvent composition, water activity, temperature, pH and alternative process routes (such as solid to solid conversions, volatile substrates or products) are investigated. This research should lead to alternative, green and sustainable production processes of fine chemicals and synthetic routes that are difficult to achieve using traditional organic chemistry. In order to further optimize and apply enzymes in bioconversion processes, fundamental knowledge of the structure-function relationship is necessary. New enzymes are isolated, purified and characterized using state of the art spectroscopic methods. Cooperation with the Bio-organic Chemistry group completes the expertise of the KIB in the field of bio- organic catalysis in aqueous and organic solvent systems.

Environmental biotechnology

The group of Microbiology and the group of Environmental Engineering are investigating novel (combinations of) microorganisms and innovative process designs to develop and optimize environmental processes. The (eco)physiological research concentrates on nitrogen and sulphur metabolism of bacteria and their function in complex systems such as waste water treatment plants. Specific attention is paid to individual growth, metabolism and metabolic control during growth on mixed substrates of (mixed) populations of microorganisms. The optimisation of wastewater treatment plants is focused on minimisation of energy input and ground area of the plant and on maximum removal efficiency of pollutants. Much effort is placed on developing the Annamox process. In this microbiological process ammonium is directly converted into nitrogen gas, thereby reducing the need for auxiliary materials and reducing the energy input of the process.

    Figure 2. One of the fermenters of the Advanced Fermentation Facilities

Bioprocess design

Bioprocess design covers a whole range of technological activities that contribute to the establishment of appropriate processes at the required production scales. Basically, in this theme models are developed that enable us to calculate local conditions (e.g. concentrations and flows) inside processing equipment. These conditions determine for example the nutrient flow to and the product flow from the biocatalysts, but also the conversion rates inside the biocatalysts (reaction kinetics). The total of local mass transfer and conversion rates determines overall process performance, and is thus important for dimensioning the equipment. It is especially important being able to predict how local conditions vary at different scales (scale up), as it is in general impossible to perform experiments in the design phase at the foreseen production scale. For composing an optimal overall process, detailed knowledge on individual processing units is used in studying the interactions between these units and to identify the bottlenecks for process design.

Analytical biotechnology

Because of the need for precise control of biochemical processes, the need for capable analytical tools is increasing. Both invasive (HPLC, CE, GC/MS) as non-invasive (NMR) techniques are used to monitor intracellular substrate, product and enzyme concentrations in a fraction of a second. Cooperation with the Faculty of Electrical Engineering and the Department of Applied Physics of the Delft University of Technology will lead to the development of micro scale detectors (analytical device on a micro chip). Professor Van Dedem has recently been appointed as part-time professor in this field of research.

Downstream processing

With the appointment of professor van der Wielen in 1997, the research on bio-separations in the Kluyver Institute is intensified even more. Special attention is paid to isolation of pure biotechnological products from multi-component mixtures. Effective processing of these aqueous mixtures with these mixed components requires a rigorous thermodynamic approach. Bringing together international experts in the field of thermodynamics and biotechnology resulted in a unique Advanced Course in Thermodynamics for Biochemical Engineers.

The research is focused on developing cleaner bioprocesses with minimum production of auxiliary materials (salts) via smooth process design (development of efficient chromatographic and adsorption techniques). Material and energy requirements are minimised.

Education in Graduate Schools

The scientific staff of the Kluyver Institute for Biotechnology takes care of a substantial part of the curriculum of the study of Chemical Engineering and Biotechnology of the Delft University of Technology in the Netherlands. Besides all biotechnological courses, education is provided in the important chemical engineering (e.g. transport phenomena) aspects. Next to this "first phase" educational activities, the Kluyver Institute plays an important role in the graduate school, Biotechnological Sciences Delft Leiden (BSDL) BSDL combines research and postgraduate education in biotechnology. It is governed jointly by Delft University of Technology, Leiden University and Wageningen Agricultural University. Biotechnology groups within the Dutch Organization for Applied Research (TNO) also contribute. Research in BSDL is divided in three sectors, industrial biotechnology, industrial plant biotechnology and environmental biotechnology. Bioprocess design functions as the integrating expertise for the three sectors. A two year advanced professional training results in the degree of Master in Biotechnology, while a two year advanced design program results in a the degree of Engineer in Bioprocess Design. Both industry and academia participate in advanced courses that are organized by BSDL. These intensive courses are given in a number of specific fields in biotechnology (Microbial Physiology and Fermentation Technology, Downstream Processing, Environmental Biotechnology, Molecular Genetics, Plant Biotechnology, Gene expression and Public Acceptance of Biotechnology).

Cooperation with the Industry

European industries participate in a large number of research projects that are performed by (clusters of) PhD-students at the KIB. Almost all research is (partially) financed by these industries. In 1998, the budget for exploitation of the Kluyver Institute for Biotechnology is approximately A$ 7.2 million. 50 % of the finance stems from the University, 10 % from scientific funds and 40 % is provided by industry. An example of industrially financed research is the ChemFerm project. Two major biotechnological companies in The Netherlands (Gist brocades and DSM) cooperate with a number of academic research groups. New environmental friendly production methods are developed for the manufacturing of semi-synthetic antibiotics. Specialised fermentation groups (in both industry and academics) search for optimised fermentation routes and try to (genetically) modify the metabolic pathways. Other groups are specialized in the enzymatic synthesis of the (new) antibiotics on the basis of the fermented building blocks.

How to contact KIB

A detailed overview of up to date research at the Institute can be found on the world wide web (http://kluyver.stm.tudelft.nl). For further information regarding the study tour please contact the organizing committee (biotour@stm.tudelft.nl).

Copyright 1998 Australian Biotechnology Association Ltd.


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