From natural products discovery to commercialization: a success story

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Abstract
In order for a natural product to become a commercial reality, laboratory improvement of its production process is a necessity since titers produced by wild strains could never compete with the power of synthetic chemistry. Strain improvement by mutagenesis has been a major success. It has mainly been carried out by “brute force” screening or selection, but modern genetic technologies have entered the scene in recent years. For every new strain developed genetically, there is further opportunity to raise titers by medium modifications. Of major interest has been the nutritional control by induction, as well as inhibition and repression by sources of carbon, nitrogen, phosphate and end products. Both strain improvement and nutritional modification contribute to the new process, which is then scaled up by biochemical engineers into pilot scale and later into factory size fermentors.