Biosynthetic convergence of salinosporamides A and B in the marine actinomycete Salinispora tropica.
[structure: see text] Feeding experiments with stable isotopes established that the potent 20S-proteasome inhibitors salinosporamide A and B are biosynthesized in the marine bacterium Salinispora tropica from three biosynthetic building blocks, namely, acetate, beta-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.
Beer
Laura L
LL
College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Moore
Bradley S
BS
D000596:Amino Acids / Q000737:chemistry; D007769:Lactams / Q000737:chemistry* / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008848:Micromonosporaceae / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D009792:Oceans and Seas; D010455:Peptides / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism*
D000596:Amino Acids; D007769:Lactams; D007783:Lactones; D010455:Peptides; D011758:Pyrroles; C475865:marizomib; C504698:salinosporamide B