Tetracyclines aromatic polyketides

An unusiul priming mechanism is observed in the biosynthetic pathway of tetracycline, one of the most important drugs in treating infectious diseases (30). Tetracyclines are aromatic polyketides synthesized by soil-borne actimonyces using type II PKS. Chlorotetracycline and oxytetracycline are biosynthesized... 

Several gene dusters encoding the enzymes of polyketide synthesis have been cloned (partially or completely). Aromatic polyketides (e.g., tetracyclines, actinorho-dine, and anthracyclines) are synthesized by type II PKSs, which are multienzyme OMn-plexes similar to FAS type II (63). In contrast, the polyketide chain of mactolide antibiotics such as erythromycin and avermectin are synthesized by PKS type I, consisting of large multifunctional polypeptides similar to FAS type I but composed of repeated units or "modules" with each active site carrying out only one reaction in the assembly and modification of each carbon chain (64,65). 

Macrolides and polyethers such as erythromycin A (4), FK 506, rapamycin or avermectin A (5, Scheme 1) are products of modular type I polyketide-synthases. These compounds are distinguished by extraordinary structural diversity and complexity [1,2]. Because of their biological potency, members of this structural class as well as the aromatic polycyclic products of type II polyketide-synthases, tetracyclines and anthara-cyclines, e.g. adriamycin (6), became useful as pharmaceuticals (antibiotics, cytostatics, immunosuppressives) [1,2],... 

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