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

Alvarez-Mico, X, Rocha DD, Guimaraes LA, Ambrose A, Chapman E, Costa-Lotufo LV, La Clair JJ, Fenical W.  2015.  The hybrid pyrroloisoindolone-dehydropyrrolizine alkaloid (-)-chlorizidine a targets proteins within the glycolytic pathway. Chembiochem. 16:2002-2006. AbstractWebsite

The cytotoxic activity of (-)-chlorizidine A, a marine alkaloid containing a unique fusion between a pyrroloisoindolone and dehydropyrrolizine, was explored by using a combination of cellular and molecular methods. Our studies began by applying preliminary SAR evidence gathered from semisynthetic bioactivity evaluations to prepare an active immunoaffinity fluorescent (IAF) probe. This probe was then used to identify two cytosolic proteins, GAPDH and hENO1, as the targets of (-)chlorizidine A.

Choi, EJ, Nam SJ, Paul L, Beatty D, Kauffman CA, Jensen PR, Fenical W.  2015.  Previously uncultured marine bacteria linked to novel alkaloid production. Chemistry & Biology. 22:1270-1279. AbstractWebsite

Low-nutrient media and long incubation times facilitated the cultivation of 20 taxonomically diverse Gram-negative marine bacteria within the phyla Bacteroidetes and Proteobacteria. These strains comprise as many as three new families and include members of clades that had only been observed using culture-independent techniques. Chemical studies of the type strains representing two new families within the order Cytophagales led to the isolation of nine new alkaloid secondary metabolites that can be grouped into four distinct structure classes, including azepinones, aziridines, quinolones, and pyrazinones. Several of these compounds possess antibacterial properties and appear, on structural grounds, to be produced by amino acid-based biosynthetic pathways. Our results demonstrate that relatively simple cultivation techniques can lead to the isolation of new bacterial taxa that are capable of the production of alkaloid secondary metabolites with antibacterial activities. These findings support continued investment in cultivation techniques as a method for natural product discovery.

Ruckert, C, Leipoldt F, Zeyhle P, Fenical W, Jensen PR, Kalinowski J, Heide L, Kaysser L.  2015.  Complete genome sequence of Streptomyces sp CNQ-509, a prolific producer of meroterpenoid chemistry. Journal of Biotechnology. 216:140-141. AbstractWebsite

Streptomyces sp. CNQ-509 is a marine actinomycete belonging to the MAR4 streptomycete lineage. MAR4 strains have been linked to the production of diverse and otherwise rare meroterpenoid compounds. The genome sequence of Streptomyces sp. CNQ-509 was found to contain 29 putative gene clusters for the biosynthesis of secondary metabolites, some of them potentially involved in the formation of meroterpenoid molecules. (C) 2015 Elsevier B.V. All rights reserved.

Leutou, AS, Yang I, Kang H, Seo EK, Nam SJ, Fenical W.  2015.  Nocarimidazoles A and B from a marine-derived actinomycete of the genus Nocardiopsis. Journal of Natural Products. 78:2846-2849. AbstractWebsite

Chemical investigation of a marine-derived actinomycete isolated from marine sediments collected off the coast of southern California and identified as a Nocardiopsis sp. (strain CNQ115) led to the isolation of two new 4-aminoimidazole alkaloids, nocarimidazoles A (1) and B (2). The chemical structures of nocarimidazoles A and B were assigned by interpretation of NMR spectroscopic data and through methylation to yield monomethyl and dimethyl derivatives. Nocarimidazoles A and B possess a 4-aminoimidazole ring combined with a conjugated carbonyl side chain, which is rarely found in microbial secondary metabolites.

Jungmann, K, Jansen R, Gerth K, Huch V, Krug D, Fenical W, Muller R.  2015.  Two of a kind: The biosynthetic pathways of chlorotonil and anthracimycin. Acs Chemical Biology. 10:2480-2490. AbstractWebsite

Chlorotonil A is a novel polyketide isolated from the myxobacterium Sorangium cellulosum So ce1525 that features a unique gem-dichloro-1,3-dione moiety. It exhibits potent bio-activity, most notably against the problematic malaria pathogen Plasmodium falciparum in the nanomolar range. In addition, strong antibacterial and Moderate antifungal activity were determined. The outstanding biological activity of chlorotonil A as well as its unusual chemical structure triggered our interest in elucidating 18 biosynthesis, a:prerequisite for alteration of the scaffold by synthetic biology approaches. This endeavor was facilitated by a recent report describing the strikingly similar structure of anthracimycin from a marine streptomycete, a compound of considerable interest due to its potent antibacterial activity. In this study, we report the identification and characterization of the chlorotonil A biosynthetic gene cluster from So ce1525 and compare It with that for anthracimycin biosynthesis. Access to both gene dusters allowed us to highlight commonalities between the two pathways and revealed striking differences, some of which Can plausibly;explain the structural differences observed between these intriguing natural products.