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

Lee, J, Han C, Lee TG, Chin J, Choi H, Lee W, Paik MJ, Won DH, Jeong G, Ko J, Yoong YJ, Nam SJ, Fenical W, Kang H.  2016.  Marinopyrones A-D, alpha-pyrones from marine-derived actinomycetes of the family Nocardiopsaceae. Tetrahedron Letters. 57:1997-2000.   10.1016/j.tetlet.2016.03.084   AbstractWebsite

Two actinomycetes, a member of the rare halophilic genus Streptomonospora and a Nocardiopsis sp. (Nocardiopsaceae), strains CNQ-082 and CNQ-675, respectively, were isolated from marine sediments collected off shore near La Jolla, California. HPLC-UV guided fractionations of the extracts of these strains yielded marinopyrones A-D (1-4), the structures of which were elucidated by interpretation of 1D and 2D NMR and HRMS spectroscopic data. Oxidative ozonation, followed by conversion of the acid product to an alpha-naphthyl amide, provided the absolute configuration at the chiral center on the side-chain. Marinopyrones A-D were examined for the inhibitory activity on nitric oxide production in LPS-activated mouse macrophage cells (RAW 264.7); marinopyrone D (4) was inhibitory with an IC50 value of 13 mu M. To our knowledge, marinopyrones A-C are only the second reported natural products from the rare halophilic genus Streptomonospora. (C) 2016 Elsevier Ltd. All rights reserved.

Le, TC, Yang I, Yoon YJ, Nam SJ, Fenical W.  2016.  Ansalactams B-D illustrate further biosynthetic plasticity within the ansamycin pathway. Organic Letters. 18:2256-2259.   10.1021/acs.orglett.6b00892   AbstractWebsite

Further chemical investigation of a marine-derived bacterium of the genus Streptomyces has led to the isolation of ansalactams B-D (1-3) along with the previously reported metabolite ansalactam A (4). Ansalactams B-D are significantly modified ansamycins, representing three new carbon skeletons and further illustrating the biosynthetic plasticity of the ansalactam class. Unlike ansalactam A, ansalactams B and D are penta- and hexacyclic metabolites, while ansalactam C illustrates an open polyene chain with a terminal carboxylic acid.

Hassan, HM, Boonlarppradab C, Fenical W.  2016.  Actinoquinolines A and B, anti-inflammatory quinoline alkaloids from a marine-derived Streptomyces sp., strain CNP975. Journal of Antibiotics. 69:511-514.   10.1038/ja.2016.56   AbstractWebsite

Actinomycete bacteria of the common genus Streptomyces can be routinely isolated from shallow and deep ocean sediments. Although commonly considered a terrestrial genus, and most abundantly found in soil, Streptomyces strains are found that have distinct requirements for seawater and routinely do not show significant similarity, with terrestrial strains by 16S ribosomal DNA phylogenetic sequence comparisons. Our examination of the culture broth of a Streptomyces sp., strain CNP975, isolated from a local La Jolla, California sediment sample, resulted in the isolation of actinoquinolines A and B (1, 2), which show significant inhibition of the arachidonic acid pathway enzymes cyclooxygenases-1 and -2. The new compounds contain the 3-hydroxyquinaldic acid (3HQA) motif found in numerous peptide antibiotics. In the actinoquinolines, 3HQA forms an amide linkage with a linear six-carbon fragment, formally a 2, 6-diamino-1, 5-dihydroxyhexane unit, a component of likely amino acid reductive off-loading origin. Actinoquinoline A illustrated amide rotational isomerism leading to complex NMR spectral data. Actinoquinoline B was assigned as the C-13 aldehyde analog isolated as an intramolecular hemiacetal. Reduction of 2 with NaBH4 yielded actinoquinoline A thus confirming the relative configurations of all centers in the actinoquinolines.

Zhou, XF, Fenical W.  2016.  The unique chemistry and biology of the piericidins. Journal of Antibiotics. 69:582-593.   10.1038/ja.2016.7   AbstractWebsite

The piericidin family of microbial metabolites features a 4-pyridinol core linked with a methylated polyketide side chain. Piericidins are exclusively produced by actinomycetes, especially members of the genus Streptomyces. The close structural similarity with coenzyme Q renders the piericidins important NADH-ubiquinone oxidoreductase (complex I) inhibitors in the mitochondria! electron transport chain. Because of the significant activities of the piericidins, which include insecticidal, antimicrobial and antitumor effects, total syntheses of the piericidins were developed using various synthetic strategies. The biosynthetic origin of this class has also been the subject of investigation. This review covers the isolation and structure determination of the natural piericidins, their chemical modification, the total syntheses of natural and unnatural analogs, their biosynthesis, and reported biological activities together with structure-activity relationships. Given the fundamental biology of this class of metabolites, the piericidin family will likely continue to attract attention as biological probes of important biosynthetic processes.

La Clair, JJ, Fenical W, Costa-Lotufo LV.  2016.  Elucidating the mode of action of marine natural products through an immunoaffinity fluorescent (iaf) approach. Journal of the Brazilian Chemical Society. 27:1346-1354.   10.5935/0103-5053.20160148   AbstractWebsite

Understanding the target and mode of action (MOA) of small molecules activity has become a critical feature in guiding the transition between drug discovery and clinical evaluation. While classically placed at the latter stages of a discovery program, we now describe how addressing the mode of action of natural products at the early stages of a program provides an important vehicle to inform the drug discovery process. In this review, we outline a streamlined cellular and molecular biological system and explore its utility through a series of four cases studies. We believe that this approach offers critical lessons to guide future drug discovery programs.