Postpolyketides

Postpolyketides are natural products whose biosynthesis begins with polyketide synthases (PKS) that assemble a carbon skeleton from simple building blocks. After the PKS chain is produced and released, a suite of tailoring enzymes installs further chemical diversity, converting the core polyketide into mature, bioactive molecules. These postpolyketide transformations may include oxidation, reduction, cyclization, dehydration, halogenation, methylation, glycosylation, and acyl or prenyl additions. The resulting products—often macrolides, polyenes, or polyether structures—are typically encoded in dedicated biosynthetic gene clusters that contain both PKS modules and a cadre of tailoring enzymes, sometimes arranged in multi-operon systems. The designation postpolyketide emphasizes that the final architecture is shaped largely by enzymes acting after chain assembly rather than by the core PKS.

Enzymes involved are diverse: cytochrome P450 monooxygenases, oxidoreductases, and other oxygenases perform site-selective oxidations; glycosyltransferases attach sugars; methyltransferases, acyltransferases, and halogenases modify functional groups; and various cyclases, epoxidases, or Diels–Alderases close rings or generate rearrangements.

The combination of core PKS chemistry with post-PKS tailoring underpins a large fraction of polyketide-derived natural products, including macrolide antibiotics, polyenes, and complex pigments. Biotechnological interest centers on manipulating tailoring steps to create novel derivatives, expanding chemical diversity and improving pharmacological properties. Genome mining and synthetic biology approaches increasingly target postpolyketide enzymes to access new compounds.