Polyketide anticancer antibiotic

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Polyketide Anticancer Antibiotic Biosynthesis 954 The Bombardier Beetle s Noxious Spray 958 Bacterial Dehalogenation of a PCB Derivative 961... 

A further natural product inhibitor is mithramydn A, a structurally complex anticancer antibiotic. Mithramycin A is a member of a group of aureolic add-type polyketides that are produced by the soil bacterium Streptomyces argillaceus [94]. 

Polyketides are an extraordinarily valuable class of natural products, numbering over 10,000 compounds. Commercially important polyketides include antibiotics (erythromycin A, tetracycline) and immunosuppressants (rapamycin), as well as anticancer (doxorubicin), antifungal (amphotericin B), and cholesterol-lowering (lovastatin) agents (Figure 25.15). It has been estimated that the sales of these and other polyketide pharmaceuticals total more than 15 billion per year. 

The polyketides are a large family of bio synthetically related NPs, some of which have very great pharmaceutical value (polyketide sales total about 10 billion annually, see also Chapter 7). Some antibiotics (erythromycin, monensin, rifamycin), immunosuppressants (rapamycin), antifungal substances (amphotericin), antiparasitic (aver-mectin) and anticancer drugs (doxorubicin) are polyketides. The term polyketide refers to the fact that the basic carbon skeleton is not a simple hydrocarbon chain as in the case of fatty acids but is a series of linked keto groups in sequence (Figure 3.6). The first phase of this pathway, the generation of carbon skeleton diversification. 

One new wrinkle on the combinatorial strategy involves a process referred to as combinatorial biosynthesis. In this situation, bacterial gene expression is altered in the hope of changing the structure and function of specific enzymes. For example, one class of potential bacteria-derived drugs are the polyketides, which may have antibiotic, immunosuppressant, and anticancer activity. Bacteria produce polyketides with the help of a family of enzymes known as polyketide synthases (PKSs). To date, most of the normally produced polyketides screened have shown little activity. 

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