[1] Curacin A belongs to a family of natural products including jamaicamide, mupirocin, and pederin that have an unusual terminal alkene.
[2][3] Curacin A has been shown to interact with colchicine binding sites on tubulin, which inhibits microtubule polymerization, an essential process for cell division and proliferation.
The synthetic enzymes for Curacin A are found in a gene cluster with 14 open reading frames (ORFs) with the nomenclature CurA through CurN.
[1][2][5] An hydroxymethylglutaryl-CoA synthase cassette (mevalonate pathway) catlyzes the formation of hydroxymethylglutaryl acid by the addition of an malonyl-CoA unit to the terminal ketide of the aceto-acetyl-ACP moiety of ACP1,ACP2, or ACP3.
[1][5][6] Seven standalone PKS modules follow to extend the growing polyketide chain with S-adenosyl methionine (SAM) dependent methylations occurring at positions 10 and 13.