Chemotherapeutic drugs (CDs) for treatment of disorders such as cancer have been traditionally originated by the isolation of natural products from different environmental niches, by chemical synthesis or by a combination of both approaches thus generating semisynthetic drugs. In the last years, a number of gene clusters from several CDs biosynthetic pathways, mainly produced by Streptomycetes and belonging to the polyketides family, are being characterized. Genetic manipulation of these CDs biosynthetic pathways offer an alternative for the generation of novel CDs derivatives. These drugs have been produced by mutagenesis and screening, protoplast fusion, targetted gene disruption, gene amplification and heterologous expression of genes in other hosts or by combinatorial biosynthesis. Here we review the production and regulation of several CDs such as erythromycin and its novel derivatives by genetic manipulation in Streptomycetes.

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