angucyclines

Angucyclines are a large class of aromatic polyketide natural products produced primarily by actinobacteria, especially Streptomyces species. They are defined by an angular tetracyclic angucyclinone core, often bearing sugar moieties and diverse oxygenated substituents. The core structure is formed by a type II polyketide synthase–based assembly that yields an angular ring system, distinguishing them from other tetracyclic polyketides.

Biosynthesis proceeds via type II PKS pathways that assemble a poly-β-keto chain, followed by cyclization and aromatization to give the angucyclinone nucleus. Tailoring enzymes—including oxygenases, glycosyltransferases, cyclases, and reductases—install hydroxyl groups, introduce ring fusions or cleavages, and attach sugars. The genes encoding these enzymes are organized in clusters that typically include the ketosynthase–like components (KSα, KSβ), an acyl carrier protein, and multiple tailoring genes; regulation of cluster expression influences production.

Many angucyclines display antibiotic or cytotoxic activities, and several act as leads for anticancer research. Notable members include landomycin A, urdamycin A, fridamycin A, and jadomycins, produced by various Streptomyces strains. Their activities and spectra vary with glycosylation patterns and oxidation state of the aglycone.

Research on angucyclines focuses on biosynthetic pathway elucidation, enzyme engineering, and combinatorial biosynthesis to generate novel derivatives and improve pharmacological properties. They remain a subject of interest for natural product discovery and drug development, reflecting the chemical diversity generated by type II PKS–mediated pathways.