evolved to form hybrids, resulting in polypeptides with nitrogen in the skeletal structure and complex function groups similar to those found in amino acids. Applications Polyketide antibiotics, antifungals, cytostatics, anticholesteremic, antiparasitics, coccidiostats, animal growth promoters and natural insecticides are in commercial use. Medicinal There are more than 10,000 known polyketides, 1% of which are known to have potential for drug activity. Polyketides comprise 20% of the top-selling pharmaceuticals with combined worldwide revenues of over USD 18 billion per year. Examples Macrolides Pikromycin, the first isolated macrolide (1951) The antibiotics erythromycin A, clarithromycin, and azithromycin The antihelminthics ivermectin Ansamycins The antitumor agents geldanamycin and macbecin, The antibiotic rifamycin Polyenes The antifungals amphotericin, nystatin and pimaricin Polyethers The antibiotic monensin Tetracyclines The antibiotic agent doxycycline Acetogenins bullatacin squamocin molvizarin uvaricin annonacin Others The immunosuppressants tacrolimus (FK506) (a calcineurin inhibitor) and sirolimus (rapamycin) (a mTOR inhibitor) Radicicol and the pochonin family (HSP90 inhibitors) The cholesterol lowering agent lovastatin Discodermolide Aflatoxin Usnic acid Anthracimycin Anthramycin Olivetolic acid (intermediate in cannabinoid pathways) Agricultural Polyketides can be used for crop protection as pesticides. Examples Pesticides spinosad or spinosyn (an insecticide) avermectin polynactins tetramycin Industrial Polyketides can be used for industrial purposes, such as pigmentation and dietary flavonoids. Examples Pigments azaphilones hydroxyanthraquinones naphthoquinones Flavonoids curcumin silymarin daidzein Biotechnology Protein engineering has opened avenues for creating polyketides not found in nature. For example, the modular nature of PKSs allows for domains to be replaced, added or deleted. Introducing diversity in assembly lines enables the discovery of new polyketides with increased bioactivity or new bioactivity. Furthermore, the use of genome mining allows for discovery of new natural polyketides and their assembly lines. See also Esterase Nonribosomal peptide ThYme (database) (2010) References NADH dehydrogenase inhibitors Plant toxin insecticides