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Blank, L

Lars M. Blank, University of Dortmund & the ISAS, Dortmund

Dr. Lars M. Blank, was born 1969 in Hilden, Germany, studied Chemical Engineering (Bioprocess Engineering) from 1990 to 1997 at the University of Dortmund (Germany) and Biology (Microbiology) from 1992 to 1997 at the Ruhr-University of Bochum (Germany) . He did his Master's thesis in the field of Metabolic Engineering in the group of Prof. E.T. Papoutsakis at Northwestern University, IL, USA. He carried out his Ph.D. project "Metabolic Engineering of Lactic Acid Bacteria" at the University of Queensland, Australia (until May 2002). During his Ph.D. he worked as a visiting scientist at the Technical University of Denmark (DtU), Lyngby, Denmark (Sept. - Dec. 1999). As a postdoctoral fellow of the Deutsche Akademie der Naturforscher Leopoldina (Halle, Germany) he established flux analysis as an additional tool for yeast Systems Biology in the group of Prof. U. Sauer at the ETH Zurich, Switzerland. Since November 2004 he has lead the Systems Biotechnology group as the chair of Chemical Biotechnology at the University of Dortmund and is a senior research fellow at the Institute for Analytical Sciences (ISAS) in Dortmund, an Institute of the Leibniz Gemeinschaft.

Dr. Blank focuses in his research on fundamental and applied aspects of microbial metabolism. Of specific interest are quantitative tools for the description of the capacity of microbial metabolism under production conditions. Such research on in silico/in vivo flux and metabolome analyses will allow the improvement of production strains for fine chemicals that are relevant for the pharma industry.

Abstract

Metabolomics for White Biotechnology

Lars M. Blank, Bruno Bühler and Andreas Schmid, University of Dortmund and the Institute for Analytical Sciences (ISAS), Dortmund, Germany

White Biotechnology is an ever growing industry that delivers chemical products for such diverse applications as agricultural chemicals, organics, plastic material and drugs, to name just a few. Advantages for the production of pharma intermediates are the high specificity (chiral, positional) that minimize or excludes unwanted byproducts. Companies involved exploit processes based on both isolated enzymes and whole cells. The latter have the advantage of self replicating catalysts and, importantly, regeneration capacity for cofactors that are necessary for a wide variety of enzyme-based reactions e.g. redox reactions.

The limitations of whole-cell biocatalysis are however numerous, include substrate/product toxicity, low biocatalytic activity, low biocatalyst concentration, and technical challenges such as oxygen transfer, and are traditionally addressed by optimizing the process conditions. With the advent of "omes", the focus shifts slowly to the smallest catalytic unit, the cell itself. Important limitations are cell population heterogeneity, enzyme availability, and cell metabolism. The capacity for cofactor regeneration for example is determined by the metabolic network, e.g. the biochemical reactions present in the cellular production host.

Here we describe the application of whole-cell biocatalysis for the production of pharmaceutical synthons. In this respect, process limitations of styrene monooxygenase containing recombinant bacteria will be discussed. We will show results indicating that biocatalyst efficiency is coupled to the energy metabolism of the host strain. Thus, studying the metabolic network by mass spectroscopy-based Fluxome and Metabolome analyses holds high potential for future strain and process optimization. This will be exemplified by solvent induced intracellular carbon flux changes in Pseudomonas strains.

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