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

Kumar, A, Borgen M, Aluwihare LI, Fenical W.  2017.  Ozone-activated halogenation of mono- and dimethylbipyrrole in seawater. Environmental Science & Technology. 51:589-595. AbstractWebsite

Polyhalogenated N-methylbipyrroles of two different structure classes have been detected worldwide in over 100 environmental samples including seawater, bird eggs, fish, dolphin blubber, and in the breast milk of humans that consume seafood. These molecules are concentrated in the fatty tissues in comparable abundance to some of the most important anthropogenic contaminants, such as the halogenated flame-retardants and pesticides. Although the origin of these compounds is still unknown, we present evidence that the production of these materials can involve the direct ozone activated seawater halogenation of N-methylbipyrrole precursors. This observation shows that environmental polyhalogenated bipyrroles can be produced via an abiotic process, and implies that the ozone activated halogenation of a variety of natural and anthropogenic seawater organics may be a significant process occurring in surface ocean waters.

Hay, AJ, Yang MH, Xia XY, Liu Z, Hammons J, Fenical W, Zhu J.  2017.  Calcium enhances bile salt-dependent virulence activation in Vibrio cholerae. Infection and Immunity. 85 AbstractWebsite

Vibrio cholerae is the causative bacteria of the diarrheal disease cholera, but it also persists in aquatic environments, where it displays an expression profile that is distinct from that during infection. Upon entry into the host, a tightly regulated circuit coordinates the induction of two major virulence factors: cholera toxin and a toxin-coregulated pilus (TCP). It has been shown that a set of bile salts, including taurocholate, serve as host signals to activate V. cholerae virulence through inducing the activity of the transmembrane virulence regulator TcpP. In this study, we investigated the role of calcium, an abundant mental ion in the gut, in the regulation of virulence. We show that whereas Ca2+ alone does not affect virulence, Ca2+ enhances bile salt-dependent virulence activation for V. cholerae. The induction of TCP by murine intestinal contents is counteracted when Ca2+ is depleted by the high-affinity calcium chelator EGTA, suggesting that the calcium present in the gut is a relevant signal for V. cholerae virulence induction in vivo. We further show that Ca2+ enhances virulence by promoting bile salt-induced TcpP-TcpP interaction. Moreover, fluorescence recovery after photobleaching (FRAP) analysis demonstrated that exposure to bile salts and Ca2+ together decreases the recovery rate for fluorescently labeled TcpP, but not for another inner membrane protein (TatA). Together, these data support a model in which physiological levels of Ca2+ may result in altered bile salt-induced TcpP protein movement and activity, ultimately leading to an increased expression of virulence.

Asolkar, RN, Singh A, Jensen PR, Aalbersberg W, Carte BK, Feussner KD, Subramani R, DiPasquale A, Rheingold AL, Fenical W.  2017.  Marinocyanins, cytotoxic bromo-phenazinone meroterpenoids from a marine bacterium from the streptomycete Glade MAR4. Tetrahedron. 73:2234-2241. AbstractWebsite

Six cytotoxic and antimicrobial metabolites of a new bromo-phenazinone class, the marinocyanins A-F (1-6), were isolated together with the known bacterial metabolites 2-bromo-1-hydroxyphenazine (7), lavanducyanin (8, WS-9659A) and its chlorinated analog WS-9659B (9). These metabolites were purified by bioassay-guided fractionation of the extracts of our MAR4 marine actinomycete strains CNS-284 and CNY-960. The structures of the new compounds were determined by detailed spectroscopic methods and marinocyanin A (1) was confirmed by crystallographic methods. The marinocyanins represent the first bromo-phenazinones with an N-isoprenoid substituent in the skeleton. Marinocyanins A-F show strong to weak cytotoxicity against HCT-116 human colon carcinoma and possess modest antimicrobial activities against Staphylococcus aureus and amphotericin-resistant Candida albicans. (C) 2017 Elsevier Ltd. All rights reserved.

Lee, HW, Choi H, Nam SJ, Fenical W, Kim H.  2017.  Potent Inhibition of Monoamine Oxidase B by a Piloquinone from Marine-Derived Streptomyces sp CNQ-027. Journal of Microbiology and Biotechnology. 27:785-790. AbstractWebsite

Two piloquinone derivatives isolated from Streptomyces sp. CNQ-027 were tested for the inhibitory activities of two isoforms of monoamine oxidase (MAO), which catalyzes monoamine neurotransmitters. The piloquinone 4,7-dihydroxy-3-methyl-2-(4-methyl-1-oxopentyl)-6H-dibenzo[b,d]pyran-6-one (1) was found to be a highly potent inhibitor of human MAO-B, with an IC50 value of 1.21 mu M; in addition, it was found to be highly effective against MAO-A, with an IC50 value of 6.47 mu M. Compound 1 was selective, but not extremely so, for MAO-B compared with MAO-A, with a selectivity index value of 5.35. Compound 1,8-dihydroxy-2-methyl-3-(4-methyl-1-oxopentyl)-9,10-phenanthrenedione (2) was moderately effective for the inhibition of MAO-B (IC50 = 14.50 mu M) but not for MAO-A (IC50 > 80 mu M). There was no time-dependency in inhibition of MAO-A or -B by compound 1, and the MAO-A and -B activities were almost completely recovered in the dilution experiments with an excess amount of compound 1. Compound 1 showed competitive inhibition for MAO-A and -B, with K-i values of 0.573 and 0.248 mu M, respectively. These results suggest that piloquinones from a microbial source could be potent reversible MAO inhibitors and may be useful lead compounds for developing MAO enzyme inhibitors to treat related disorders, such as depression, Parkinson's disease, and Alzheimer's disease.

Yang, I, Yoon J, Kim D, Hahn D, Nam SJ, Fenical W.  2017.  4Z- and 4E-12-deoxydihydrokromycins, two naturally occurring kromycin aglycones of pikromycin from Streptomyces sp. Tetrahedron Letters. 58:2322-2324. AbstractWebsite

HPLC-UV guided isolation for the culture broth extract of the marine-derived bacterium Streptomyces sp. has led to the two 14-membered macrolides, 4Z- (1) and 4E-12-dehydroxykromycins (2). The chemical structures of compounds 1 and 2 were elucidated by spectral data, while the absolute stereochemistry of 1 and 2 were determined by application of circular dichroism (CD) and analysis of X-ray crystallographic data. (C) 2017 Published by Elsevier Ltd.