Strain improvement for production of pharmaceuticals and other microbial metabolites by fermentation.

Microbes have been good to us. They have given us thousands of valuable products with novel structures and activities. In nature, they only produce tiny amounts of these secondary metabolic products as a matter of survival. Thus, these metabolites are not overproduced in nature, but they must be overproduced in the pharmaceutical industry. Genetic manipulations are used in industry to obtain strains that produce hundreds or thousands of times more than that produced by the originally isolated strain. These strain improvement programs traditionally employ mutagenesis followed by screening or selection; this is known as 'brute-force' technology. Today, they are supplemented by modern strategic technologies developed via advances in molecular biology, recombinant DNA technology, and genetics. The progress in strain improvement has increased fermentation productivity and decreased costs tremendously. These genetic programs also serve other goals such as the elimination of undesirable products or analogs, discovery of new antibiotics, and deciphering of biosynthetic pathways.