polyketide

Polyketides are a large and diverse class of secondary metabolites produced by bacteria, fungi, and plants. They are built by polyketide synthases (PKS) through successive condensations of acetyl-CoA and malonyl-CoA extender units, with optional reductions, dehydrations, and cyclizations that create a wide variety of carbon skeletons. PKS enzymes are categorized into three main types: type I modular PKSs, common in many bacteria and fungi, that assemble products in an assembly-line fashion; type II iterative PKSs, which use a smaller set of domains repeatedly for each round of chain elongation; and type III plant PKSs, typically homodimeric enzymes that generate simpler polyketide rings.

The products include macrolides (e.g., erythromycin), aromatic and polycyclic polyketides, polyenes (e.g., amphotericin B), and macrolide immunosuppressants (e.g., tacrolimus, sirolimus) as well as statins (e.g., lovastatin) produced by microorganisms. The biological activities are broad, with roles as antibiotics, antifungals, anticancer agents, immunosuppressants, and cholesterol-lowering drugs. Biosynthetic gene clusters encode not only the PKS enzymes but also tailoring enzymes such as ketoreductases, dehydratases, methyltransferases, and glycosyltransferases that diversify final products. A common feature is the use of an acyl carrier protein to hold growing chains and a thioesterase or cyclase to release the mature polyketide.

Polyketides are important targets in natural product research and drug discovery due to their structural diversity and wide range of biological activities.