Polyketide synthase

The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis.

The growing chain is handed over from one thiol group to the next by trans-acylations and is released at the end by hydrolysis or by cyclization (alcoholysis or aminolysis).

[16] Polyketides are a large family of natural products widely used as drugs, pesticides, herbicides, and biological probes.

[19] This bias is commonly explained with the argument that natural products have co-evolved in the environment for long time periods and have therefore been pre-selected for active structures.

Molecular evidence supports the notion that many novel polyketides remain to be discovered from bacterial sources.

Reaction mechanisms of type I, II and III PKSs. Decarboxylation of malonyl unit followed by thio-Claisen condensation. a) (cis-AT) type I PKS with acyl carrier protein (ACP), keto synthase (KS) and acyl transferase (AT) domains covalently bound to another . b) Type II PKS with KSα-KSβ heterodimer and ACP as separate proteins. c) ACP-independent Type III PKS.
Biosynthesis of the doxorubicin precursor, є-rhodomycinone. The polyketide synthase reactions are shown on top.