Natural occurrence, bioactivity, and biosynthesis of triene-ansamycins.

Triene-ansamycins such as ansatrienins and cytotrienins are characterized by three conjugated double bond motifs within a 21-membered benzenoid ansamycins. Their structural diversity exists in the different substituents in the C-11 or C-13 side chain or in the 3-amino-5-hydroxy benzoic acid moiety. More complex derivatives have been reported with fused ring systems which may be produced via intramolecular cycloaddition between phenol and triene. The biosynthetic gene clusters and biosynthetic pathway of ansatrienins and cytotrienins have been characterized. Based on biosynthetic knowledge, a series of structural analogs has been prepared by genomic manipulation. Triene-ansamycins exhibit significant anticancer activity. The structure-activity relationships and biological targets have been investigated. This mini-review presents a comprehensive survey of triene-ansamycins, which covers natural occurrence, biological activity, biosynthesis, structural derivatization, structure-activity relationships, and biological targets from 1967 to 2022. Eighty triene-ansamycins have been reported.