Distinguished Professor of Oceanography

Research Interests

  • Chemistry of marine plants, microorganisms and invertebrate animals.
  • Utilization of marine-derived compounds for the treatment of various human diseases, in particular cancer and infectious diseases.

Degrees

  • B.S., California State Polytechnic University
  • M.S., San Jose State University
  • Ph.D., University of California, Riverside

Recent Publications

Nakatsuji, T, Chen TH, Butcher AM, Trzoss LL, Nam SJ, Shirakawa KT, Zhou W, Oh J, Otto M, Fenical W, Gallo RL.  2018.  A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Science Advances. 4 AbstractWebsite

We report the discovery that strains of Staphylococcus epidermidis produce 6-N-hydroxyaminopurine ( 6-HAP), a molecule that inhibits DNA polymerase activity. In culture, 6-HAP selectively inhibited proliferation of tumor lines but did not inhibit primary keratinocytes. Resistance to 6-HAP was associated with the expression of mitochondrial amidoxime reducing components, enzymes that were not observed in cells sensitive to this compound. Intravenous injection of 6-HAP in mice suppressed the growth of B16F10 melanoma without evidence of systemic toxicity. Colonization of mice with an S. epidermidis strain producing 6-HAP reduced the incidence of ultraviolet-induced tumors compared to mice colonized by a control strain that did not produce 6-HAP. S. epidermidis strains producing 6-HAP were found in the metagenome from multiple healthy human subjects, suggesting that the microbiome of some individuals may confer protection against skin cancer. These findings show a new role for skin commensal bacteria in host defense.

da Silva, RM, Guaratini T, Jimenez PC, Fenical W, Costa-Lotufo LV, Vessecchi R, Lopes NP.  2018.  Mass spectrometry analysis of protonated marine natural product seriniquinone. Journal of the Brazilian Chemical Society. 29:1162-1166. AbstractWebsite

Seriniquinone is a natural quinone isolated from a rare marine bacterium of the genus Serinicoccus. This secondary metabolite has been shown to have anticancer properties, which has raised attention of the scientific community. In this short report, we present the first investigation of the gas-phase chemistry fragmentation reactions of seriniquinone in electrospray ionization tandem mass spectrometry (ESI-MS/MS), to be further applied in pharmacokinetics and metabolism studies. All the proposals herein were supported by computational chemistry.

Zheng, J, McKinnie SMK, El Gama A, Fengit W, Dong Y, Agarwal V, Fenical W, Kumar A, Cao ZY, Moore BS, Pessah IN.  2018.  Organohalogens naturally biosynthesized in marine environments and produced as disinfection byproducts alter sarco/endoplasmic reticulum ca2+ dynamics. Environmental Science & Technology. 52:5469-5478. AbstractWebsite

Contemporary sources of organohalogens produced as disinfection byproducts (DBPs) are receiving considerable attention as emerging pollutants because of their abundance, persistence, and potential to structurally mimic natural organohalogens produced by bacteria that serve signaling or toxicological functions in marine environments. Here, we tested 34 organohalogens from anthropogenic and marine sources to identify compounds active toward ryanodine receptor (RyR1), known toxicological targets of non-dioxin like polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). [H-3]Ryanodine ([H-3]Ry) binding screening (<= 2 mu M) identified 10 highly active organohalogens. Further analysis indicated that 2,3-dibromoindole (14), tetrabromopyrrole (31), and 2,3,S-tribromopyrrole (34) at 10 mu M were the most efficacious at enhancing [H-3]Ry binding. Interestingly, these congeners also inhibited microsomal sarcoplasmic/endoplasmic reticulum (SR/ER) Ca2+ ATPase (SERCA1a). Dual SERCAla inhibition and RyR1 activation triggered Ca2+ efflux from microsomal vesicles with initial rates rank ordered 31 > 34 > 14. Hexabromobipyrroles (25) enhanced [H-3]Ry binding moderately with strong SERCAla inhibition, whereas pyrrole (24), 2,3,4-tribromopyrrole (26), and ethyl-4-bromopyrrole-2-carboxylate (27) were inactive. Of three PBDE derivatives of marine origin active in the [H-3]Ry assay, 4'-hydroxy-2,3',4,5',6-pentabromodiphenyl ether (18) was also a highly potent SERCAla inhibitor. Molecular targets of marine organohalogens that are also DBPs of emerging environmental concern are likely to contribute to their toxicity.

Leutou, AS, Yang IH, Le TC, Hahn D, Lim KM, Nam SJ, Fenical W.  2018.  Fluvirucin B6, a new macrolactam isolated from a marine-derived actinomycete of the genus Nocardiopsis. Journal of Antibiotics. 71:609-612. AbstractWebsite

A new 14-membered macrolactam natural product, fluvirucin B6 (1), was isolated from a marine-derived actinomycete, Nocardiopsis sp. CNQ-115, via HPLC-UV guided isolation. The chemical structure of 1 was elucidated by 1D and 2D NMR spectroscopic data analysis. Compound 1 showed a weak activity against Gram-positive bacteria, whereas it was inactive against Gram-negative bacteria.

Yim, CY, Le TC, Lee TG, Yang I, Choi H, Lee J, Kang KY, Lee JS, Lim KM, Yee ST, Kang H, Nam SJ, Fenical W.  2017.  Saccharomonopyrones A-C, New alpha-Pyrones from a Marine Sediment-Derived Bacterium Saccharomonospora sp CNQ-490. Marine Drugs. 15 AbstractWebsite

Intensive study of the organic extract of the marine-derived bacterium Saccharomonospora sp. CNQ-490 has yielded three new ff-pyrones, saccharomonopyrones A-C (1-3). The chemical structures of these compounds were assigned from the interpretation of 1D, 2D NMR and mass spectrometry data. Saccharomonopyrone A (1) is the first ff -pyrone microbial natural product bearing the ethyl-butyl ether chain in the molecule, while saccharomonopyrones B and C possess unusual 3-methyl and a 6-alkyl side-chain within a 3,4,5,6-tetrasubstituted alpha-pyrone moiety. Saccharomonopyrone A exhibited weak antioxidant activity using a cation radical scavenging activity assay with an IC50 value of 140 mu M.