Metabolic engineering and directed evolution for the production of pharmaceuticals.
The tools of metabolic and enzyme engineering have been well developed in academic laboratories and are now being applied for the optimization of biocatalysts used in the production of a wide range of pharmaceutically important molecules. Engineered microorganisms with a diverse set of modified or non-native enzyme activities are being used both to generate novel products and to provide improved processes for the manufacture of established products, such as in the production of precursors, intermediates, and complete compounds 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 for the development and selection of mutated enzymes with improved properties. A variety of such methods have been used to alter the activity, stability 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 exciting challenge for process scientists today.
Chartrain
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M
Merck Research Laboratories, BIOPROCESS R&D, Merck & Co, Inc, PO Box 2000, Rahway, NJ 07065, USA.
Salmon
P M
PM
Robinson
D K
DK
Buckland
B C
BC
D000596:Amino Acids / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019020:Directed Molecular Evolution; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D005658:Fungi / Q000235:genetics / Q000378:metabolism; D005818:Genetic Engineering; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis; D014815:Vitamins / Q000096:biosynthesis / Q000235:genetics
D000596:Amino Acids; D004792:Enzyme Precursors; D009097:Multienzyme Complexes; D004364:Pharmaceutical Preparations; D013256:Steroids; D014815:Vitamins; D010453:Peptide Synthases