Technische Universität Braunschweig – made-to-measure synthetic microorganisms
The Institute of Biochemical Engineering at Technische Universität Braunschweig (Technical University (TU) Braunschweig) is a member of the Biopolymers/Biomaterials cluster and, as such, is involved in two projects to produce diaminopentane and succinic acid using optimised microorganisms with the aim of establishing a basis from which to provide industry with new materials made from renewable resources.
One of the Institute of Biochemical Engineering's (ibvt) major goals is the development of made-to-measure cell factories. The institute is part of the TU Braunschweig and is directed by Prof. Dr. Christoph Wittmann, a biotechnologist who has a great deal of experience in this field, notably from his doctoral thesis. "While I was doing my doctoral thesis, I became fascinated with the complex inner life of microorganisms and finding ways to alter it in order to make it suitable for biotechnological applications," said Wittmann who was awarded the Young Scientist Award of the European Biotechnology Association in 2005 for his work. After successful habilitation at Saarland University and a temporary position at the University of Münster, Wittmann returned to the TU Braunschweig in 2008.
The ibvt is mainly focused on investigating the specific use of microorganisms for the sustainable production of biobased chemicals and materials. This work very much depends on the ibvt's interdisciplinary activities. "We are an institute that bridges the gap between the life- and engineering sciences," said Professor Wittmann whose 50-member research team includes experts from the fields of bioprocess engineering, biotechnology, bioengineering, bioprocess engineering, biology, molecular biology and chemistry.
Creating an optimal strain in the laboratory
"We use systems biotechnology methods to find out how the microbial metabolism works," said Wittmann further explaining that these investigations involve methods such as metabolic flow analysis. Prof. Wittmann compares this process with a city: "We look at the city and the flow of traffic from above; we observe people on their way to work and look at whether construction sites block the traffic flow. And we do the same thing with cells; we look into the cells, analyse the large number of signalling pathways in order to obtain insights into the pathways used by cells to produce things." As a result of these observations and analyses, the ibvt scientists are able to genetically modify the bacterial metabolism, a process that is referred to as metabolic engineering. This enables high yields of sought-after metabolites to be produced. Once the optimal strain has been created in the laboratory, the ibvt engineers go on to optimise the fermentation process to achieve the best possible bioproduction for use in industrial application.
The ibvt researchers have recently published two papers on research involving Corynebacterium glutamicum. Since the 1970s, the amino acid lysine, which is used as a feedstuff additive, has been produced by fermentation in quantities of around 1 million t/y. Up until now, the production strains have been produced by random mutagenesis and have the disadvantage that they contain many negative mutations. This makes them very sensitive to stress with the result that they grow relatively slowly. Using systems biology methods, the ibvt researchers have now been able to construct a Corynebacterium strain whose genome has only 12 mutations. This bacterial strain produces 120 g lysine per litre of culture in around 24 h. "This is a major advance and we are very proud of our achievements," said Wittmann.
Cluster project with great potential for the future
Additional mutations enabled the scientists to programme the cells in order to be able to convert lysine into diaminopentane, which is highly interesting for the production of innovative biobased products. The modified cells are able to produce 80 g of diaminopentane per litre in a relatively short time.
In a cooperative project of the Biopolymers/Biomaterials cluster, the ibvt are working with BASF SE, Daimler AG, Robert Bosch GmbH and fischerwerke GmbH & Co. KG to produce a biopolyamide that is suitable for industrial applications. The innovative biopolyamide PA5.10 has already been used by the fisher group of companies to produce wall plugs. "The polyamide was used and thoroughly tested in normal production cycles," said Wittmann. In another cluster project, the ibvt researchers led by Wittmann are working with BASF SE to produce biosuccinic acid, which is another highly interesting platform chemical due its broad range of applications. "Biosuccinic acid has great potential for the future," said Wittmann. Succinic acid can be used for the production of butanediol, tetrahydrofuran and polyesters. As part of the project, the ibvt, with its partner BASF SE, is also concentrating on the use of renewable resources. Christoph Wittmann is well aware of the huge interest in sustainable products. "We are heading towards a biobased society," said the biotechnologist.
The cluster's seminal model projects have successfully demonstrated how petrochemical processes can be replaced with sustainable bioprocesses. The only obstacle, as Wittmann points out, is the price of biologically produced bulk chemicals, which is currently quite high. "However, it is important that we continue to focus on the technology and show that it possible to replace petrochemical processes with biological ones," said Wittmann.
At the ibvt, systems biotechnology methods are also a crucial factor in the production of active compounds. The collaborative research centre (Sonderforschungsbereich, SFB 578) "Development of biotechnological processes by integrating genetic and engineering methods - from genes to products" and the SFB TR-51 "Systems biology of marine microorganisms" synthesise products with a therapeutic effect such as antibodies, bone growth factors and antibiotics.