Meeting report: New biotechnological production systems


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The increasing shortage of fossil resource and global climate change today demand fundamental innovation and new concepts in bioprocess development for the production of commodities (chemicals) and fuels from renewable resources. Currently, bioproduction of commodities and fuels in large scale is almost exclusively based on microbial systems, primarily in form of pure culture. Despite great achievements in the past, the microbial production system has several inherent limitations.

First, due to the underlying principle of balanced oxidation and reduction of bioreactions the theoretical yield of a typical fermentation product is at the best limited to about 50% by weight of the substrate. A major part of the substrate is converted into CO2 and other waste or toxic byproducts. Second, microorganisms have evolved and are optimized in nature mainly for growth and survival, but not for the synthesis of a certain metabolite, limiting the achievable concentration of a desired product due to limited product tolerance in most cases.

Despite great achievements in the past, the microbial production system has several inherent limitations

Adding the fact that microbial bioconversion takes place almost in aqueous solution, the cost for recovery and purification of the products is often high. From the perspective of strain and process optimization, the cell wall represents a physical barrier for efficient control and manipulation. Despite impressive progress in molecular biology and more recently in genomic approaches, systems and synthetic biology, a purposeful and exact control of intracellular processes under production conditions is in many cases still very difficult. Another major drawback of present bioproduction systems based on pure culture is that they can normally use only a single substrate or a simple mixture of substrates. These facts impose severe economic and ecological constraints on industrial biotechnology aimed at producing chemicals and fuels from abundant and complex substrates such as cellulose and hemicelluloses.

Biorefinery has been proposed as a new concept for next generation bioproduction system

Biorefinery has been proposed as a new concept for next generation bioproduction system for chemicals, materials, fuels and energy and is being intensively investigated worldwide. However, except for a more complete use of (complex) substrates, the other three inherent limitations of present bioproduction systems as mentioned above are not sufficiently addressed. In fact, the individual steps or unit operations of contemporary biorefinery processes remains often inefficient, limiting the realization of the promise of this concept. The needs for more fundamental innovation and new concepts in bioproduction systems have been increasingly recognized by the scientific community and political decision makers. For example, the German Federal Ministry for Ed ucation and Research (BMBF) has recently started a Strategy Process “Nächste Generation biotechnologischer Verfahren – Biotechnologie 2020+” (“Next Generation of Biotechnological Processes – Biotechnology 2020+”) (http://www.biotechnologie The German Society for Chemical Engineering and Biotechnology (DECHEMA Gesellschaft für Chemische Technik und Biotechnologie e. V.) has correspondingly planned to set up a new ad hoc working party (Arbeitskreis) on “New Biotechnological Production Systems”. As part of the preparation for establishing this new working party, a workshop with the same name as the working party took place on May 8, 2011 in Frankfurt am Main under the umbrella of DECHEMA.

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The workshop aimed to provide insights into the major concepts and potentials of novel bioproduction systems as an alternative to the currently established ones as well as approaches that may deserve re-visiting. Internationally renowned scientists and representatives from both academia and industry were invited to discuss the needs and challenges for future research and development. Prof. Jim Swartz (Stanford University, CA, USA) gave the first plenary lecture entitled “Cell-free technologies: Past, present and future”. In this very well perceived lecture he reviewed not only the potential and achievements of cell-free synthesis of proteins, but also the latest developments in the application of cell-free technologies for the production of chemicals and bioenergy (e.g. from sun light and CO2) was presented. Critical issues for future development were addressed. The process examples presented by Prof. Swartz clearly demonstrate that cell-free bioproduction systems are also of high interest for chemicals and bioenergy. In the subsequent presentation “Eukaryotic cell-free protein synthesis: In vitro translation of membrane proteins and glykoproteins” given by Dr. Stefan Kubick (Fraunhofer Institute for Biomedical Engineering, Potsdam, Germany) it was shown that cell-free protein expression systems have recently developed as promising tools for rapid and efficient production of a wide variety of membrane proteins. In particular, a novel eukaryotic in vitro translation system was presented for glycosylation of expressed membrane proteins. This new in vitro system expands the possibilities of cell-free protein synthesis for a better control of posttranslational modifications of proteins.

The workshop aimed to provide insights into the major concepts and potentials of novel bioproduction systems

In another intellectually stimulating plenary lecture delivered by Dr. Roland Wohlgemuth (Sigma-Aldrich, Switzerland) new bioproduction systems for the synthesis of metabolites and intermediates were discussed from an industrial perspective. In particular, recent developments of novel biocatalytic reactions for the synthesis of metabolites and intermediates were illustrated with several concrete examples. In the presentation of Matthias Bujara from the group of Prof. Sven Panke (ETH Zürich, Switzerland), cell-free systems for fine chemicals were addressed, especially for optically pure or phosphorylated compounds. For this purpose multi-enzyme reaction systems are normally needed. The challenges and possible solutions for efficiently carrying out such biosynthesis systems were demonstrated with the production of dihydroxyacetone phosphate, which involves a ten-enzyme reaction network.

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Not only cell-free but also new cell-based production systems were covered in this workshop. Prof. Nediljko Budisa (Technical University of Berlin, Germany) illustrated the reprogramming of protein synthesis in cells by genetic code engineering. This method enables the production of proteins with non-natural amino acids. With three product examples, Prof. Budisa demonstrated that this novel synthetic biology approach can lead to bioproduction systems and products with a wide range of applications in industrial and pharmaceutic biotechnologies. Prof. Vera Meyer (Technical University of Berlin, Germany) highlighted recent breakthroughs in fundamental and applied research in Aspergillus. New concepts and challenges in future development of Aspergillus as a multi-purpose cell factory were discussed. In the closing presentation entitled “Next generation bioproduction systems for commodities and fuels” given by myself, the inherent limitations of present bioproduction systems were illustrated. Examples of new bioproduction systems, which have the potential to overcome some of the inherent limitations of present bioproduction systems were presented. The examples included both cell-based and cell-free systems for chemicals and bioenergy and can be characterized as nature-inspired, synthetic, modular, miniaturized and integrated respectively. These features may be viewed as key concepts for developing the so-called next generation of bioproduction systems and as a resume of the workshop. To this end, fundamental innovations and new tools are desperately needed.