Metabolic engineering and directed evolution for the production of pharmaceuticals

The tools of metabolic and enzyme engineering have been well developed in a cademic laboratories and are now being applied for the optimization of bioc atalysts used in the production of a wide range of pharmaceutically importa nt molecules. Engineered microorganisms with a diverse set of modified or n on-native enzyme activities are being used both to generate novel products and to provide improved processes for the manufacture of established produc ts, such as in the production of precursors, intermediates, and complete co mpounds of importance to the pharmaceutical industry, including polyketides , nonribosomal peptides, steroids, vitamins, and unnatural amino acids. The use of directed evolution has rapidly emerged to be the method of choice f or the development and selection of mutated enzymes with improved propertie s. A variety of such methods have been used to alter the activity, stabilit y and availability of an array of enzymes. The industrial practice of these technologies at large scale is, however, in its infancy and stands as an e xciting challenge for process scientists today.