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Nam, SJ, Kauffman CA, Paul LA, Jensen PR, Fenical W.  2013.  Actinoranone, a cytotoxic meroterpenoid of unprecedented structure from a marine adapted streptomyces sp. Organic Letters. 15:5400-5403.   10.1021/ol402080s   AbstractWebsite

The isolation and structure elucidation of a new meroterpenoid, actinoranone (1), produced by a marine bacterium closely related to the genus Streptomyces is reported. Actinoranone is composed of an unprecedented dihydronaphthalenone polyketide linked to a bicyclic diterpenoid. The stereochemistry of 1 was defined by application of the advanced Mosher's method and by interpretation of spectroscopic data. Actinoranone (1) is significantly cytotoxic to HCT-116 human colon cancer cells with an LD50 = 2.0 mu g/mL.

Nam, SJ, Gaudencio SP, Kauffman CA, Jensen PR, Kondratyuk TP, Marler LE, Pezzuto JM, Fenical W.  2010.  Fijiolides A and B, Inhibitors of TNF-alpha-Induced NF kappa B Activation, from a Marine-Derived Sediment Bacterium of the Genus Nocardiopsis. Journal of Natural Products. 73:1080-1086.   10.1021/np100087c   AbstractWebsite

Fijiolide A, a potent inhibitor of TNF-alpha-induced NF kappa B activation, along with fijiolide B. were isolated from a marine-derived bacterium of the genus Nocardiopsis. The planar structures of fijiolides A (1) and B (2) were elucidated by interpretation of 2D NMR spectroscopic data, while the absolute configurations of these compounds were defined by interpretation of circular dichroism and 2D NMR data combined with application of the advanced Mosher's method. Fijiolides A and B are related to several recently isolated chloroaromatic compounds, which appear to be the Bergman cyclization products of enediyne precursors. Fijiolide A reduced TNF-alpha-induced NE kappa B activation by 70.3%, with an IC(50) value of 0.57 mu M. Fijiolide B demonstrated less inhibition, only 46.5%, without dose dependence. The same pattern was also observed with quinone reductase (QR) activity: fijiolide A was found to induce quinone reductase-1 (QR1) with an induction ratio of 3.5 at a concentration of 20 mu g/mL (28.4 mu M). The concentration required to double the activity was 1.8 mu M. Fijiolide B did not affect QR1 activity, indicating the importance of the nitrogen substitution pattern for biological activity. On the basis of these data, fijiolide A is viewed as a promising lead for more advanced anticancer testing.

Nam, SJ, Kauffman CA, Jensen PR, Moore CE, Rheingold AL, Fenical W.  2015.  Actinobenzoquinoline and actinophenanthrolines a-c, unprecedented alkaloids from a marine actinobacterium. Organic Letters. 17:3240-3243.   10.1021/acs.orglett.5b01387   AbstractWebsite

Chemical investigation of a marine actinomycete within the family Streptomycetaceae (our strain CNQ-149) has led to the isolation of the unprecedented alkaloids, actinobenzoquinoline (1) and actinophenanthrolines A-C (2-4). The chemical structures of 1-4 were assigned by interpretation of NMR spectroscopic data, and their absolute configurations were assigned by X-ray analysis. Actinobenzoquinoline possesses a 5-methyloxazolidin-4-one moiety and a dihydrobento[h],quinoline core structure, while actinophenanthrolines A-C are composed of hydroxypropanamide-substituted 1,7-phenanthroline core skeletons.

Nam, SJ, Kauffman CA, Jensen PR, Fenical W.  2011.  Isolation and characterization of actinoramides A-C, highly modified peptides from a marine Streptomyces sp. Tetrahedron. 67:6707-6712.   10.1016/j.tet.2011.04.051   AbstractWebsite

Reported herein is the isolation and structure elucidation of three highly modified peptides, actinoramides A-C (1-3), which are produced by a marine bacterium closely related to the genus Streptomyces. The planar structures of the actinoramides, which are composed of the unusual amino acids 2-amino-4-ureidobutanoic acid and 4-amino-3-hydroxy-2-methyl-5-phenylpentanoic acid, were assigned by chemical transformations and by interpretation of spectroscopic data, while the absolute configuration of these new peptides were defined by application of the advanced Marfey's and Mosher's methods. (C) 2011 Elsevier Ltd. All rights reserved.

Newbold, RW, Jensen PR, Fenical W, Pawlik JR.  1999.  Antimicrobial activity of Caribbean sponge extracts. Aquatic Microbial Ecology. 19:279-284.   10.3354/ame019279   AbstractWebsite

Marine sponges produce a diversity of unusual chemical compounds, but the ecological functions of these metabolites remain largely unknown. To determine if sponge secondary metabolites have ecologically significant antimicrobial effects, organic extracts from 33 species of Caribbean sponges were assayed for antibiotic activity against a test panel of marine bacteria. The test panel consisted of 8 strains representing 6 genera of marine bacteria and included an opportunistic pathogen (Vibrio parahaemolyticus), a common fouling bacterium (Deleya marina), and strains isolated from seawater and healthy and necrotic Caribbean sponges. Extracts were tested for antibiotic activity at concentrations that were volumetrically equivalent to those found in sponge tissues (whole-tissue concentrations). Bioassay results revealed that 16 species (48 %) exhibited antibiotic activity against at least 1 bacterial isolate and that the 2 bacteria isolated from necrotic sponge tissues were the most sensitive test strains (inhibited by 40 % of the extracts). Extracts from Amphimedon compressa, Amphimedon erina, Aplysina lacunosa, and Ptilocaulis spiculifera inhibited the largest numbers of test strains and exhibited the most potent antibiotic activities with values frequently exceeding those of a control antibiotic (gentamicin). The pattern of antimicrobial activity was different for 15 of 16 active sponge species, suggesting that diverse taxa do not produce similar antibacterial metabolites. Overall, only 23 % of the extract/bacterial interactions exhibited antibacterial activity, indicating that, in general, conspicuous members of the Caribbean sponge community do not produce broad-spectrum antibacterial metabolites. All of the species yielding antibacterial extracts also deterred feeding by reef fishes in a previous study, suggesting that some secondary metabolites may have evolved multiple defensive functions. Stevensine, a compound from Axinella corrugata (=Teichaxinella morchella) known to deter feeding by predatory reef fishes, exhibited weak antimicrobial activity, suggesting that this potent feeding deterrent is not solely responsible for the antimicrobial activity detected in the crude sponge extract.

Newton, GL, Jensen PR, MacMillan JB, Fenical W, Fahey RC.  2008.  An N-acyl homolog of mycothiol is produced in marine actinomycetes. Archives of Microbiology. 190:547-557.   10.1007/s00203-008-0405-3   AbstractWebsite

Marine actinomycetes have generated much recent interest as a potentially valuable source of novel antibiotics. Like terrestrial actinomycetes the marine actinomycetes are shown here to produce mycothiol as their protective thiol. However, a novel thiol, U25, was produced by MAR2 strain CNQ703 upon progression into stationary phase when secondary metabolite production occurred and became the dominant thiol. MSH and U25 were maintained in a reduced state during early stationary phase, but become significantly oxidized after 10 days in culture. Isolation and structural analysis of the monobromobimane derivative identified U25 as a homolog of mycothiol in which the acetyl group attached to the nitrogen of cysteine is replaced by a propionyl residue. This N-propionyl-desacetyl-mycothiol was present in 13 of the 17 strains of marine actinomycetes examined, including five strains of Salinispora and representatives of the MAR2, MAR3, MAR4 and MAR6 groups. Mycothiol and its precursor, the pseudodisaccharide 1-O-(2-amino-2-deoxy-alpha-Dglucopyranosyl)-Dmyo-inositol, were found in all strains. High levels of mycothiol S-conjugate amidase activity, a key enzyme in mycothiol-dependent detoxification, were found in most strains. The results demonstrate that major thiol/disulfide changes accompany secondary metabolite production and suggest that mycothiol-dependent detoxification is important at this developmental stage.