title: Antiprotealide is a natural product.
abstract: Large-scale fermentation of the marine actinomycete Salinispora tropica for production of salinosporamide A (NPI-0052; 1) clinical trials materials provided crude extracts containing minor secondary metabolites, including salinosporamide B (2) and a new congener, 3. Spectroscopic characterization revealed that 3 is identical to antiprotealide, a molecular hybrid of 20S proteasome inhibitors 1 and omuralide (4) not previously described as a natural product. Analysis of crude extracts from shake flask cultures of three wild-type S. tropica strains confirmed the production of antiprotealide at 1.1, 0.8, and 3.0 mg/L. Thus, antiprotealide is a natural product metabolite of S. tropica.
authors.affiliation: Nereus Pharmaceuticals, Inc, 10480 Wateridge Circle, San Diego, California 92121, USA.
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Manam
authors.forename: Venkat R
authors.initials: VR
authors.lastname: Macherla
authors.forename: Ginger
authors.initials: G
authors.lastname: Tsueng
authors.forename: Chris W
authors.initials: CW
authors.lastname: Dring
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weiss
authors.forename: Saskia T C
authors.initials: ST
authors.lastname: Neuteboom
authors.forename: Kin S
authors.initials: KS
authors.lastname: Lam
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Potts
mesh_terms: D039903:Actinobacteria / Q000737:chemistry*; D000818:Animals; D001688:Biological Products / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D008386:Marine Biology; D015394:Molecular Structure; D046988:Proteasome Endopeptidase Complex; D011758:Pyrroles / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D011817:Rabbits
chemical_list: D001688:Biological Products; D007769:Lactams; D007783:Lactones; D011758:Pyrroles; C531354:antiprotealide; C117645:omuralide; C475865:marizomib; D046988:Proteasome Endopeptidase Complex