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Biocatalysis is an important subspecialty of white biotechnology. At BASF they are used primarily to produce chiral intermediates required for the production of medicines and crop protectants.
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From chiral compound to enzyme
Chirality means "handedness". Any molecule that cannot be superimposed on its mirror image is chiral ("handed"). Chiral compounds have identical physical properties but usually produce different biological effects. For example, one of the chiral forms of the amino acid asparagine is a sweetener, whereas the other tastes bitter. Living organisms automatically synthesize such molecules in one form only, in contrast to synthesis by chemical engineering processes, in which the molecules are simultaneously produced in the two chiral forms. This is because enzymes in living organisms quite selectively prefer one form over the other in the biological conversion process. BASF takes advantage of this principle in the biocatalytic manufacture of substances in technical plants.
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In biocatalysis the entire microorganism is frequently not used in the manufacturing process. The enzyme that produces the desired substance is removed from the cell and used as a catalyst for the technical manufacture of chiral compounds. BASF is one of the first companies to use biocatalytic processes on a large scale in the manufacture of chiral intermediates. Some of them are produced on an individual customized basis and sold under the trade name ChiPros®. BASF brought two production plants – in Ludwigshafen, Germany, and Geismar, Louisiana – on stream in 2001. We are ceaselessly looking for new enzymes in order to be able to manufacture more chiral products.
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How do we find new enzymes?
Today it is assumed that approximately 1% of the microorganisms occurring in nature can be cultured in the laboratory. These organisms and the species which are as yet unknown are bearers of a correspondingly large number of enzymes. It is assumed that many reactions can be performed with appropriate enzymes (biocatalysts) although technical application may only be possible in the distant future. The challenge lies in discovering biocatalysts for the desired substance transformations and adapting them to the requirements of a chemical production plant. For instance, we already have the technology for isolating DNA from soil organisms and examining it for new enzyme activities. We developed this technology in collaboration with the University of Stuttgart and the Fraunhofer Institute of Biotechnology in Stuttgart.
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Evolution in a test tube
Enzymes in their natural state are usually inappropriate for direct use in a biocatalytic process. They may be too unstable or of restricted activity. We have therefore adopted nature’s strategy, evolution. New, modified enzyme activities are produced by mutation and selection. The biocatalysts obtained in this manner will allow many new biotechnical processes in the fields of intermediates and specialty chemicals. In particular, the high selectivity of enzyme catalysts will simplify processes significantly and thus result in reduced manufacturing costs.
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