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European Biopharmaceutical Review

The Protein Production Line

Clemens Achmüller and Bernhard Auer at the Austrian Center of Biopharmaceutical Technology, Institute of Biochemistry, University of Innsbruck, Austria investigate fusion protein technology for expression of therapeutic proteins and peptides in E coli

The production of therapeutic proteins requires rapid, efficient and cost effective expression and purification strategies. Moreover, the design of such strategies has to be developed for each protein or peptide individually. More generally, applicable expression systems, which are not driven by the individual protein, would substantially reduce the time for product development. Fusion protein technology represents one way to achieve these goals, by enhancing protein expression, reducing protein degradation, assisting proper folding, facilitatating purification and, in some cases, generating protein with a native N-terminus. Hence, protein fusion techniques are a primary option to manufacture therapeutic proteins and peptides, especially in E coli, which is still a widely-used host in industrial scale production. This review covers recent developments in protein fusions for periplasmic expression and expression in the cytoplasm in soluble form. Further focus will be on the production of fusion proteins in inclusion bodies and a newly developed method of autoprotease fusion technology.

In the production of biopharmaceuticals, E coli has been the longstanding workhorse due to its simplicity, low cost and high productivity. Only the need for specific modification of proteins (such as glycosylation) has driven researchers and production facilities towards more costly higher organisms like baculovirus and mammalian cell culture systems. A major problem in reducing the costs for product development in the pharmaceutical industry is the invariably long time and high cost of clinical testing and evaluation of efficacy of the drug.


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Clemens Achmüller gained his PhD from the University of Innsbruck with work on the development of protein expression systems, based on viral autoproteases in 2006 (with Bernhard Auer). He is now a postdoctoral fellow in the Institute of Biochemistry at Innsbruck.

Bernhard Auer has been a Chemist and Professor of Biochemistry at the University of Innsbruck, Austria, since 1988. Starting from E coli phage genetics he worked for about two decades on DNA-repair processes in mammalian cells. Around 2000 he returned to the E coli system where he now focuses on protein expression systems.

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Clemens Achmüller
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Bernhard Auer
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