Salinispora

Mincer TJ, W Fenical, PR Jensen (2005) Culture-dependent and culture-independent diversity within the obligate marine actinomycete genus Salinispora. Appl Environ Microbiol 71 7019-7028. 

OMe Marine bacteria - Streptomyces sp. and Salinispora arenicola Cyciomarins A-D - peptides with anti-infiammatory property 83, 84... 

Salinosporamide A (84), a y-lactam alkaloid isolated from marine actinomycete Salinispora tropica also proved to possess strong antimalarial activity both in vitro (IC50 11.4 nM) and in vivo ... 

Feling RH, Buchanan GO, Mincer TJ, Kauffman CA, Jensen PR, Fenical W. (2003) Salinosporamide A A highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus Salinispora. 

The Palauan deep-water (500 m) marine actinomycete Salinispora pacifica has yielded cyanosporasides A (1731) and B (1732), which feature a chlorine on an unactivated benzene ring (1658). The authors suggest a novel biosynthesis from an enediyne precursor. Related to the previously known nosto-cyclophanes (1) are the new carbamidocyclophanes A-E, of which A (1733), B (1734), C (1735), and D (1736) are chlorinated, being isolated from the Vietnamese cyanobacterium Nostoc sp. (1659). These compounds exhibit cytotoxicity against MCF-7 (breast) and FI (amniotic epithelial) human cancer cells. 

Reed KA, Manam RR, Mitchell SS, Xu J, Teisan S, Chao T-H, Deyanat-Yazdi G, Neuteboom STC, Lam KS, Potts BCM (2007) Salinosporamides D-J from the Marine Actinomycete Salinispora tropica, Bromosalinosporamide, and Thioester Derivatives Are Potent Inhibitors of the 20S Proteasome. J Nat Prod 70 269... 

Buchanan GO, Williams PG, Feling RH, Kauffman CA, Jensen PR, Fenical W (2005) Sporolides A and B Structurally Unprecedented Halogenated Macrolides from the Marine Actinomycete Salinispora tropica. Org Lett 7 2731... 

Organism Streptomyces coelicolor A3(2)40 S. griseus IFO 1335042 Salinispora tropica CNB-4405 Mycobacterium tuberculosis H37Rv43 Frankia sp. CcI344 N. farcinica IFM 1015245... 

Udwary DW, Zeigler L, Asolkar RN, Singan V, Lapidus A, Fenical W, Jensen PR, Moore BS (2007) Genome Sequencing Reveals Complex Secondary Metabolome in the Marine Acti-nomycete Salinispora tropica. Proc Natl Acad Sci USA 104 10376... 

Salinosporamides Salinispora tropica Inhibitors of proteasome function and cytotoxic activity (tumor cells)... 

The marine bacterial metabolite salinosporamide A (39) was isolated from the totally new genus Salinispora that mapped to the Micromonosporaceae, which are found in marine sediments across the tropics. It demonstrated activity as a cytotoxic protea-some inhibitor (62) similar to that observed for the structurally related compound omuralide (40) (63, 64), which resulted from a spontaneous rearrangement of the microbial metabolite lac-tacystin in neutral aqueous media. Salinosporamide has been synthesized (65, 66) and has been fermented in saline media on a large scale under cGMP conditions. It entered Phase I clinical trials in May 2006. 

Jensen PR, et al. Species-specific secondary metabolite production in marine actinomycetes of the genus Salinispora. Appl. Environ. Microbiol. 2007 73 1146-1152. 

Udwary DW, et al. Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica. Proc. Natl. Acad. Sci. U.S.A. 2007 104 10376-10381. Edwards DJ, et al. Structure and biosynthesis of the ja-maicamides, new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula. Chem. Biol. 2004 11 817-833. 

Recent pursuit of marine microbial sources led to the isolation of salinosporamide A (83). It is a P-lactone produced by the marine bacteria Salinispora tropica and is a proteasome inhibitor (86). Mechaiustically, it works by specific covalent modification of the target. This compound has entered human cliiucal development for treatment of multiple myeloma (87-89). 

The potently cytotoxic proteasome inhibitor salinosporamide A (26, NPI-0052) was isolated from a new genus of marine bacteria called Salinispora The bicyclic (/3-lactam-7-lactam) core structure of salinosporamide A is also found in the activated form of lactacystin known as r/iMto-lactacystin /3-lactone (24, omuralide). While structurally similar to omuralide, salinosporamide A (26) is pharmacologically and mechanistically distinct/ Unlike omuralide, chloride displacement from the chlorinated side chain in salinosporamide A... 

Salinosporamide A, NPI 0052, a microbial product of Salinispora tropica strain CNB-392 that acts as a potent protea-some inhibitor. Salinosporamide A is structurally related to omuralide, the -lactone derived from lactacystin, and is more effective as a proteasome inhibitor than omuralide. Furthermore, it exhibits cytotoxicity against many tumor cell lines, especially against Velcade resistant multiple myeloma cells [V. Caubert, N. Langlois, Tetrahedron Lett. 2007, 48, 381]. 

Moore and co-workers recently reported the identification of the prenyl transferase CymD from the marine actinobacterium Salinispora arenicola, which catalysed N-ferf-prenylation of L-tryptophan prior to its incorporation into the cyclic... 

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