Jeffrey L. Wright
Carl B. Brown Distinguished Professor, Department of Marine Science
- B.Sc., University of Glasgow, Scotland
- Ph.D., University of Glasgow, Scotland
Our group is focused on the isolation, chemical characterization, and biosynthesis of bioactive natural products obtained from our unique and expanding collection of culturable marine microorganisms. These include both photosynthetic microalgae and non-photosynthetic bacteria, and represent a diverse collection of organisms and chemistries.
Nearly 50 % of today’s pharmaceuticals are derived from natural products. Almost all of them are derived from land-based organisms. In the search for new chemical structures possessing important biological activity, we have turned to culturable marine organisms as the source organisms. At the UNCW Center for Marine Science, we maintain almost 400 marine derived bacteria and 300 marine microalgae, and through an international collaboration with another research organization we have access to an additional 2,000 marine microbes.
Searching these organisms for new chemical compounds has been fruitful and to date around 100 new compounds have been isolated, purified, characterized, and logged in our compound library. These compounds are put through a series of biological screens to determine their full biological profile. In addition to this we are archiving the chemical extracts of all these organisms as fractions stored in 96-well plates for convenient high throughput screening. Each year, as the culture collection expands, the fractions from these extracts are added to this compound library.
Another area of long-standing interest to us has been the isolation and characterization of marine toxins produced by various genera of marine microalgae, usually dinoflagellates. These microalgae or phytoplankton can form massive blooms in the ocean which are often referred to as “red tides”. Most recently we have characterized several new polyether compounds produced by the dinoflagellate Karenia brevis which is known to produce the brevetoxins. These new compounds, known as brevisamide and brevisin, are non-toxic but provide valuable information as to how these complex polyethers are biosynthesized by the dinoflagellate. More recently we have characterized a new family of amphipathic toxins produced by the dinoflagellate Karlodinium veneficum which is linked to fish kills. The karlotoxins are very similar to another group of amphipathic toxins known as the amphidinols which are produced by a group of dinoflagellates belonging to the genus Amphidinium. These compounds are extremely large and complex in structure but we have recently published the structure and biosynthesis of AM 17, yet another addition to this intriguing group of hemolytic and antifungal compounds.
The biosynthesis of all of the compounds we examine continues to be both fascinating and challenging. Through innovative stable isotope labeling studies we have determined the building blocks and characterized the biosynthetic pathways that lead to the production of many of these compounds. Often we have described new and unexpected biosynthetic pathways. The ultimate goal of this work is to identify the biosynthetic genes required for the production of these complex secondary metabolites, with a view to controlling their production and modifying the genes to produce new chemical compounds.
Short List of Research and Publications
Yanhui Meng, Ryan M. Van Wagoner, Ian Misner, Carmelo Tomas, and Jeffrey L. C. Wright. Structure and Biosynthesis of Amphidinol 17, a Hemolytic Compound from Amphidinium carterae. J. Nat Prods. In press (2009)
Rochfort, Simone J.; Moore, Stanley; Craft, Cheryl; Martin, Ned H.; Van Wagoner, Ryan M., Wright, Jeffrey L. C. Further Studies on the Chemistry of the Flustra Alkaloids from the Bryozoan Flustra foliaceae. Journal of Natural Products72:1773-1781 (2009).
Satake, M., Campbell, A., Van Wagoner, R.M., Bourdelais, A.J., Jacocks, H., Baden, D.G., and Wright, J.L.C. Brevisin: An aberrant polycyclic ether structure from the dinoflagellate Karenia brevis and its implications for polyether assembly. J. Org. Chem. 74: 989-994 (2009).
Wright, Jeffrey L. C. Fish and shellfish toxins. Microbiology Handbook: Fish and Seafood Toxins. (Rhea Fernandes editor). 141-174 (2009).
Kuranaga, T., Shirai, T., Baden, D.G., Wright, J.L.C., Satake, M. and Tachibana, K. Total synthesis and structural confirmation of Brevisamide, a new marine cyclic ether alkaloid from the dinoflagellate Karenia brevis. Org. Letts. 11: 217-220 (2009).
Satake, Masayuki; Bourdelais, Andrea J.; Van Wagoner, Ryan M.; Baden, Daniel G.; Wright, Jeffrey L. C. Brevisamide: an unprecedented monocyclic ether alkaloid from the dinoflagellate Karenia brevis that provides a potential model for ladder-frame initiation
Organic Letters10,3465-3468 (2008)
Meng, Y., Krzysiak, A.J., Durako, M.J., Kunzelman, J.I. and Wright, J.L.C. Flavones and flavone glycosides from Halophila johnsonii. Phytochem 69: 2603-2608 (2008).
Van Wagoner, R.M., Deeds, J.R., Satake, M., Ribeiro, A.A., Place A.R. and Wright, J.L.C. Isolation and characterization of karlotoxin 1, a new amphipathic toxin from Karlodinium veneficum. Tetrahedron Letters 49: 6457-6461 (2008).
Van Wagoner, R.M., Mantle, P.G. and Wright J.L.C. Biosynthesis of scorpinone, a 2-azaanthraquinone from Amorosia littoralis, a fungus from marine sediment. J. Nat. Prods. 71: 426-430 (2008).
Bouillon, R.-C., Kieber, R.J., Skrabal, S.A. and Wright J.L.C. Photochemistry and identification of photodegradation products of the marine toxin domoic acid. Mar. Chem. 110: 18-27 (2008).
Van Wagoner, R.M., Drummond, A.K. and Wright, J.L.C. Biogenetic diversity of cyanobacterial metabolites. Adv. Appl. Microbiol. 61: 89-217 (2007).
Mayer, K.M., Ford, J., MacPherson, G.R., Padgett, D., Volkmann-Kohlmeyer, B., Kohlmeyer, J., Murphy, C., Douglas, S.E., Wright, J.M. and Wright, J.L.C. Exploring the diversity of marine-derived fungal polyketide synthases. Can. J. Microbiol. 53: 291-302 (2007).
Lail, E.M., Skrabal, S.A., Kieber, R.J., Bouillon R.-C. and Wright, J.L.C. The role of particles on the biogeochemical cycling of domoic acid and its isomers in natural water matrices. Harmful Algae 6: 651-6557 (2007).
Bouillon, R.-C., Kneirim, T.L., Kieber,R.J., Skrabal, S.A and Wright, J.L.C. Photodegradation of the algal toxin domoic acid in natural water matrices. Limn. and Oceanog. 51: 321-330 (2006).
Wright, J.L.C. and Kralovec, J. A nutritional supplement for lowering serum triglyceride and cholesterol levels. U.S. 6998501 B1 20060214 (2006).
Bourdelais, A.J., Jacocks, H.M., Wright, J.L.C., Bigwarfe, P.M. Jr. and Baden, D.G. A new polyether ladder compound produced by the dinoflagellate Karenia brevis. J. Nat. Prod. 68: 2-6 (2005).
Kunzelman, J.L.,Durako, M.J., Kenworthy, W.J., Stapelton, A. and Wright, J.L.C. Irradiance-induced changes in the photobiology of Halophila johnsonii. Marine Biology 148: 241-250 (2005).
MacKenzie, S.E., Gurusamy, G.S., Piorko, A., Strongman,D.B., Hu, T. and Wright, J.L.C. Isolation of sterols from the marine fungus Corollospora lacera. Can. J. Microbiol. 50: 1069-1072 (2004).
MacPherson, G. P., Burton, I. W., LeBlanc, P., Walter, J. A. and Wright, J. L. C. Studies of the biosynthesis of DTX-5a and DTX-5b by the dinoflagellate Prorocentrum maculosum; regiospecificity of the putative Bayer-Villagerase and insertion of a single amino acid in a polyketide chain. J. Org. Chem. 68: 1659-1664 (2003).