Of considerable interest are the recently discovered ß-alkylation events involving an HMG-CoA synthase (HCS)-like gene and associated tailoring domains embedded within PKS/NRPS pathways. To date, several biosynthetic gene clusters for the production of secondary metabolites containing that type of genetic architecture have been reported, such as curacin A, jamaicamide A, B and C, mupirocin, bacillaene, pederin, and myxovirescin. Each have been annotated as having stand alone homologs of the HCS and a set of genes encoding one or more ACPs, a mutant ketosynthase with a cys-to-ser active site substitution (KSs) and two homologs of the enoyl-CoA hydratase (ECH₁ and ECH₂) family. It is known that these gene products condense acetyl-CoA with the ß-ketoacyl-S-ACP intermediate of the growing polyketide to eventually result in the addition of the C2 acetate carbon in the structure. Furthermore, elaboration upon that carbon has yielded diverse functionalities including a pendant methyl group in bacillaene and mupirocin, a cyclopropyl ring in curacin A, and a vinylic chloride in jamaicamide A. A biochemical investigation of the genes and enzymes that prescribe the addition of the C2 of acetate onto the polyketide backbone of jamaicamide A, resulting in a vinyl chloride group in will be discussed. The focus of this system involves investigations of the HCS-ECH-ECH-ER motif and the halogenase enzyme in the jamaicamide pathway. Preliminary results reveal differential mechanistic activity of ECH₁ and ECH₂ as well as a highly unexpected chlorinated intermediate.