Polyketides

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As polyketides refers to a large group of natural compounds that their chemical structures and pharmacological properties is extremely composed heterogeneous with respect. What they have in common is biosynthesis via the so-called polyketide route . Numerous polyketides are of great importance as drugs , including antibiotics such as tetracyclines or erythromycin , the cancer drugs doxorubicin and epothilone, and the anti- parasite drugs avermectins .

biosynthesis

Special enzyme complexes , the polyketide synthases , form precursors of the polyketides from simple, coenzyme A -activated acyl groups (mostly acetyl-CoA , malonyl-CoA ). Depending on the number of acyl-CoAs involved in the synthesis, one can speak of tetraketides (four), pentaketides (five) etc. This step-by-step chain elongation is similar to fatty acid synthesis . In contrast to this, however, a reduction to an aliphatic chain only rarely takes place. Each acetyl building block of the chain can remain at various stages of the modifications that theoretically lead to the fatty acid (keto group> hydroxyl group> double bond> single bond). Further enzyme reactions (e.g. cyclization, methylation or oxygenation) complete the biosynthesis of the polyketides.

Orsellic acid biosynthesis

Structural diversity

Structure of erythromycin A

The diversity and complexity can be seen in a few examples: One of the simplest polyketides is 6-methylsalicylic acid . Of a more complex nature flavonoid plant dyes such as quercetin , the mycotoxins zearalenone , Alternariol or aflatoxins , the macrolide antibiotic erythromycin or polyene - antifungal drug amphotericin B (also a macrolide ). Particularly complex structures occur in the polyketides of marine organisms, e.g. B. with maitotoxin or palytoxin .

literature

  • Gerhard Habermehl, Peter E. Hammann, Hans C. Krebs, natural product chemistry. 2nd edition, Springer Verlag, 2002, ISBN 3-540-43952-8 .
  • Peter Nuhn: Natural Products Chemistry. Microbial, vegetable and animal natural substances. 2nd edition, S. Hirzel Wissenschaftliche Verlagsgesellschaft Stuttgart, 1990, ISBN 3-7776-0473-9 .

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