Insilico is designing Formula One-type bacteria

21 August 2007

Insilico Biotechnology AG in multi-year collaboration with Wacker Chemie AG to design high-performance bacterial strains

(Stuttgart) — Insilico Biotechnology AG is set to become one of the partners in the GenoMik-Plus network. The Stuttgart-based company will provide the partners of the research consortium with network models and simulations of the bacterial metabolism. The objective is to develop high-performance bacterial strains that produce large amounts of useful substances.

The manufacturing industry benefits from model calculations and simulations which are computer-generated, i.e. in silico. The computer takes over a lot of development work, both cheaply and quickly, simulates possibilities for enhancing the quality and yield and makes accurate predictions. This is a technique that is also increasingly used in the area of white biotechnology in which microorganisms are used for the large-scale production of fine chemicals, food and feed additives, technical enzymes and biofuels.

One such example is the production of amino acids for the food industry. A leader in this sector is Wacker Chemie AG who are using high-performance strains of the E. coli bacteria to produce cystein. Wacker is one of the industrial partners in the BMBF-funded GenoMik-Plus network who are hoping to advance biotechnological production methods. In order to be able to exploit the bacterial strains to an even greater extent, Wacker has called on Insilico Biotechnology AG for help.

»Cystein is still mainly produced from animal raw materials, including bird feathers, pig bristles and human hair. Since the pharmaceutical and food industries are becoming more and more sensitive to products of human and animal origin, Wacker Chemie’s microbial production method has a clear advantage«, said the head of biotechnological research at Wacker, Dr. Günter Wich, who is hoping to work with Insilico to enhance the efficiency of high-performance strains and make them even more competitive.

Exact model and simulation of the metabolism

The first thing the Insilico experts are doing is to reconstruct the bacteria’s metabolism on the computer, based on genome data. »The wild-type of the bacteria is already available as a computer model and approximately 90 percent of all genes involved in the E. coli metabolism can be modelled in connection with metabolic reactions,« said Insilico CEO Klaus Mauch. However, the wild-type does not produce more cystein than required for its own use. Therefore, the computer models have to be altered so as to make them as similar to the production strains as possible.

There are two further phases: specific computer programmes will be used to make predictions about production-enhancing alterations in the metabolism. Inventions at production-relevant key positions in the metabolism will be modelled and the effects on the efficiency of production calculated. In the second phase, there will be laboratory investigations to find out what actually happens following genetic manipulation of the strains. This part of the project will be carried out by the Wacker laboratory team. Transcription and metabolics data will be acquired, which Mauch and his team will integrate into the virtual network in order to analyse. »This phase is very time-consuming because we are cross-checking with the experimental work,« said Mauch.

Genetic »tuning«: Turning bacteria into high-performance producers

»The overall process is iterative; rational strain development needs to go through several cycles of such phases and for as long as is required to obtain a satisfactory result,« said the company boss. This process not only provides the scientists with findings that can potentially be patented but also with a considerable technological lead. Instead of waiting to see what kind of evolutive changes will happen and cultivating particularly productive strains, the development of the bacterial strains will be accelerated using mechanistic predictions. »We are interested in bringing the decision process forward,« said Mauch.

Cystein is the first amino acid to be produced with this method but Mauch hopes to transfer the method to other biotech productions and strengthen his activities in the GenoMik-Plus network, which focuses on the general expansion of the microbial production potential using genome-based research. Mauch is in contact with other GenoMik-Plus network partners: »I think we are at the beginning of a wave which will become visible in about two to three years time. In the field of white biotechnology, a degree of networking will be achieved that is unique in Germany. And this is just starting to happen,« said Mauch commenting on the further development of industrial production using microorganisms.

Insilico platform can be used for many substrates and products

Insilico has set out to actively accompany this development and advance it with systems biological knowhow. The company not only relies on amino acids, Mauch also envisages the microbiological production of biofuels. Insilico has the expertise as well as the soft- and hardware to model the most suitable metabolic activities required to turn certain substrates into certain products. Mauch also names the processing of lignocelluloses into butanol as an application with a high future potential. Butanol is an alcohol that can be used as fuel.

Mauch is specifically interested in substances that might accrue in increasing amounts as part of biofuel production, for example glycerol. »Glycerol is produced as a side product during the production of bioethanol and is an excellent and cheap substrate for microbial production. Currently, the amount of glycerol produced per year amounts to 800,000 tons. Our instruments enable us to simulate the set-up of the bacterial cell required for the efficient processing of glyercol,« said Mauch.

The results of the models and simulations are available to the partners for research and development within the scope of the GenoMik-Plus network. For Insilico to be able to react quickly to further inquiries, the company is working to establish the main »workhorses« of biotech production. Besides E. coli these are yeasts and lactic acid bacteria. »We already have Bacillus subtilis and a number of other species and it seems that we will soon be able to comprehensively simulate corynebacteria,« added Mauch.

© BIOPRO Baden-Württemberg GmbH, Article first published at www.bio-pro.de, the Biotech/Life Sciences Portal of the state Baden-Württemberg. All rights reserved.

Contact

Insilico Biotechnology AG
Klaus Mauch (CEO)
Nobelstrasse 15
70569 Stuttgart, Germany
Phone +49 711 65696661
info [at] insilico-biotechnology.com
www.insilico-biotechnology.com