Möglichkeiten zur gezielten Manipulation der Genexpression des mikrobiellen Sekundärstoffwechsels

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Abstract
The present review deals with some theoretical and applied aspects of directed manipulations of control mechanisms governing the expression of microbial secondary metabolism. In attempting to make broad generalizations, the production of secondary metabolites is discussed in terms of the cellular differentiation of relevant organisms. On the basis of the actual information about the regulation of microbial idiolite synthesis, some potential ways for the quantitative and the qualitative improvement of secondary metabolite production are discussed. A number of examples demonstrate the effectiveness of rational strategies of strain development, e. g., the removal of non-specific repressions of secondary metabolism by environmental factors, the excessive production of precursors due to altered control of intermediary metabolism, the increased resistance of producer organism against the autotoxicity of some idiolites, the deletion of alternative pathways of the primary and secondary metabolism, manipulations concerning the product spectrum, the deletion of feedback mechanisms, and elimination of degradating pathways in the secondary metabolism etc. The scope and limitations of rational strategies of strain improvement by genetic and physiologic manipulations are subjected to final discussion.