Structures of the Other Aeo-containing Peptides
These cyclic peptides all contain four amino acids. One of the amino acids is either proline or the homolog pipecolic acid. All contain Aeo (2-amino-9,10-epoxi-8-oxodecanoic acid) except apicidin, which lacks the epoxide group.
All are made by filamentous fungi. HC-toxin is made by the maize pathogen Cochliobolus carbonum; Cyl-2 is made by the plant pathogen Cylindrocladium scoparium (now known as Calonectria pteridis); WF-3161 is made by the saprophyte Petriella guttulata; trapoxin A is made by the saprophyte Helicoma ambiens; chlamydocin by the saprophyte (perhaps nematode parasite?) Diheterospora chlamydosporia; and apicidin byFusarium semitectum. The biosynthetic gene cluster for apicidin biosynthesis has been recently characterized (Jin et al., 2010, Mol Microbiol 76:456-66). It shows a high degree of similarity to TOX2 of C. carbonum for HC-toxin biosynthesis.
All of these cyclic peptides, including apicidin, are potent inhibitors of histone deacetylases (HDAC). An affinity column based on trapoxin was used for the first isolation of a histone deacetylase (Taunton et al., 1996, Science 272:408), starting the 'modern era' of HDAC research.