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ATG:biosynthetics GmbH – Modular molecular systems of the future

Although synthetic biology is still in its infancy, it nevertheless has the potential to revolutionise the world economy. ATG:biosynthetics GmbH, based in Merzhausen close to Freiburg, produces biological systems that can combine gene constituents following a construction kit principle. The company provides the pharmaceutical industry and basic researchers with products that have specifically chosen properties. The company also provides assistance in using these tailor-made proteins and genes in areas such as multigene co-expression, immunodiagnostics and the investigation of cellular signalling networks. Dr. Hubert Bernauer, ATG:biosynthetics GmbH’s managing director, is convinced that in the long term, the sustainable chemistry, energy and food industries will also benefit from these modular molecular systems. However, he also believes that politicians need to adopt a different attitude.

 "Any politician who cares about green issues should be enthusiastic about synthetic biology, but ideological blindness prevents this from being the case," said Dr. Hubert Bernauer. Synthetic biology enables the assembly of specific genes and proteins with sought-after properties. Bernauer is convinced that no other technology can be integrated and harmonised with the earth's substance cycles in such a smart and efficient way. As it stands, biologists might soon be able to modify microorganisms and plants in ways that enable them to produce more biomass for the production of energy and food without releasing toxic gasses into the atmosphere. This is exactly the reason why Bernauer is focusing on synthetic biology, which, in addition, is able to remove CO2 from the air. In net terms, it is only the energy of the sun that flows through the systems; all substances produced from biomass can be returned to the substance cycle. "Since the beginning of time, nature has been doing what synthetic biologists will be able to do one day in the future," said Bernauer. "What we are doing is merely plugging into natural substance cycles. Unlike the petrol industry, we do not produce extra COnor do we contaminate the oceans." Doctors also stand to benefit from synthetic biology as they will be able to reprogramme defective cells (for example cancer cells) as well as use synthetic biology to diagnose and treat many other diseases (for example metabolic diseases).

Synthetic biology is actually reversed bionics

The schematic shows how multiprotein complexes can be created through cloning and recombination (system for the bacterium Escherichia coli). © ATG:biosynthetics GmbH

ATG:biosynthetics GmbH offers biological systems that can be used to assemble complex proteins and genes. Basically this works in a similar way to a popular children's toy: individual DNA fragments are assembled in test tubes in a precisely defined order, rather like Lego bricks. However, the functionality of some of these constructs needs to be optimised using functional "fine tuning". It is not quite as simple as it seems to develop biological nanoworlds of this kind. Sequences that code for certain protein regions can be incorporated with other regions into plasmids. This leads to combined genes, or so-called gene cassettes. The ATG specialists can introduce these cassettes into bacterial, insect and mammalian cells, and in future they will also be able to introduce them into yeast cells. The protein molecules encoded by the newly synthesised genes can then be expanded in these organisms and large quantities of the sought-after substances can be produced.

Example of a multiprotein complex: SRP complex bound to a ribosome. Reconstruction of the complex based on cryo-electron microscope images. © Dr. Christine Schaffitzel, EMBL Grenoble

Researchers at universities and in the pharmaceutical industry can use these cassettes to create complex proteins with a clearly defined structure that do not occur in natural organisms. "Synthetic biology is actually reversed bionics," said Bernauer. "We do not use things that occur in nature such as the principle found in lotus leaves where water droplets roll off like mercury, and transfer these principles into technological applications. What we do is to transfer technical principles, for example standardisation, to nature, before taking individual components, modifying them and turning them into something completely new. Nature does this every day on the molecular level to create new forms of life completely at random. Synthetic biology works less randomly, we have clear ideas of what we want to create."

Pipetting unit of a pipetting robot, a device that is indispensable for carrying out high-throughput experiments. © Dr. Imre Berger, EMBL Grenoble

Such ideas include molecule systems that are able to alter the metabolic and signalling processes in a cell. For example, if researchers want a cell to produce a certain substance (for example a drug) via an external signal, they will be able to do so one day in the future using synthetic biology. "However, we can also support our clients in the application of these systems in certain projects," said Bernauer. Initially, ATG mainly focussed on the synthesis of genes. Over the last few years, the company has changed its business model, and Bernauer and his five colleagues have become specialists in multiprotein syntheses, the design of signalling and artificial biochemical synthesis pathways as well as the production of functional multiprotein complexes. The ATG team also support their clients in the selection and application of synthetic biological components. ATG is a suitable interface in the development of applications in the field of bio-industrial automation and robotics since its kits and the underlying processes can be automated. ATG works alongside leading companies in the field of biorobotics.

Moral commitment of all those involved

One of Bernauer’s goals is to make synthetic biology methods safer. “Genetic engineering is already one of the safest technologies known,” said Bernauer. “When it has been accurately and thoroughly considered, no hazards attributed to the use of genetic engineering have ever occurred. Recent thinking on the subject has been of a theoretical and potential nature and only describes hypothetical damage potential, which of course we would always seek to prevent. The media give transgenes a bad reputation when it describes them as toxins.” The goal of synthetic biology is to create modular genetic systems that interact as little as possible with natural systems but that at the same time are compatible with natural degradation pathways. When one looks at it more closely, it is not genetic engineering that makes people afraid, but rather its abuse, in particular on the markets (dependence on big companies) and its criminal misuse, for example by terrorists. Bernauer is a member of the IASB (International Association of Synthetic Biology), which is currently working on developing safety standards in the field. A “code of conduct”, a moral commitment involving all those who work in academic or private sector synthetic biology research, has already been launched and is recognised around the world. This will ensure that new methods become reliable and useful tools in a bio-based industry that is paving the way out of a petrochemical past.

However, in Germany synthetic biology is still in its infancy and is currently very susceptible to the harsh winds blowing in the global markets. “German politicians are still pursuing a wrong strategy,” said Bernauer, an ex-pupil of a business grammar school. He speaks from experience. He studied molecular genetics, biochemistry, microbiology and organic chemistry in Freiburg and spent his postdoctoral period in the Department of Oncology at the University Hospital in Mainz, where he filed a patent for a method enabling the synthesis of genes, which he developed during his doctoral period. The strategic orientation of ATG is based on this principle. Bernauer founded ATG in 2001 after he was forced to sell GeneScan Europe AG, which he co-founded, as a result of the dotcom crises on the “New Market” in Frankfurt. “We must not destroy young markets through high subsidies,” warns Bernauer going on to add that it is necessary to fund young companies, but that this support must be market oriented and must not lead to a decline in the prices charged for services offered by private companies.

Market rules must be taken seriously

Bernauer also says that the growing number of services and products offered by market participants that receive government funding also leads to a huge distortion of competition. In his view, the politically sought-after, direct interconnection of public institutes with big industry in some German states is a governmental directivism that levers out medium-sized biotechnological companies. These offers have the same effect on the economy as that of cooperatives in the past. “Since subsidised young companies often operate below required real market prices, this destroys the market prices,” said the biologist. “The companies that are obliged to operate according to market rules will end up going bankrupt.” Bernauer also said that globalisation and the strong euro are further reasons why biotechnology in Germany is not as economically well developed as that of countries outside the EU. According to Bernauer, the biggest mistake that is being made in Germany is that the companies receive no support until such time as they reach market stability. Once companies have finalised the development of a product or a service, they are left to deal with market introduction of these products and services on their own, which often leaves them without any money to focus on the comprehensive market introduction due to the enormous sums that they have already spent on product development. The companies run out of steam before they are able to tap the money cycles.

It is for these reasons that Bernauer became involved in the TESSY project (Towards a European Strategy for Synthetic Biology). The group of European Union-funded specialists is committed to turning synthetic biology into a strong economic factor in Europe. “However, this will only be possible once politicians understand that the market rules have to be taken seriously,” said Bernauer. “We must reject a subsidy culture that is based on the scientific origin of synthetic biology and move towards a market-oriented investment culture such as in the USA. Only then will we become successful market participants in a global market and only then will we have a chance to succeed on international markets.”

Further information:
Dr. Hubert S. Bernauer
ATG:biosynthetics GmbH
Weberstr. 40
79249 Merzhausen
Tel.: +49-(0)761/8889424
Fax: +49-(0)761/8889425
Mobile: +49-(0)179/6607141
E-mail: info(at)ATG-biosynthetics.de



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