Salinosporamide A


potent 20S-proteasome inhibitors salinosporamide A and B are biosynthesized in the marine bacterium Salinispora tropica from three biosynthetic building blocks, namely, acetate, -hydroxy-2'-cyclohexenylalanine, and either butyrate or a tetrose-derived chlorinated molecule. The unexpected observation that the chlorinated four-carbon residue in salinosporamide A is derived from a different metabolic origin than the non-chlorinated four-carbon unit in salinosporamide B is suggestive of a convergent biosynthesis to these two anticancer natural products.