Current Projects
The Marine Natural Products Group at the University of Prince Edward Island is engaged in projects directed at the development of sustainable production methods of bioactive marine metabolites and discovering new bioactive bioproducts. The latter group includes metabolites with activities in assays of relevance to human health and with activity as antifouling agents.
Our discovery program encompasses both macroorganisms (e.g. sponges, tunicates, octocorals, algae) and microbes as sources of bioactive compounds. These organisms are collected from diverse marine habitats in the Caribbean and Atlantic Canada. The library of fractionated extracts generated from these collection programs is screened through a variety of bioassays many of which are collaborative projects with groups at UPEI, NRC-INH, McGill University as well as industrial partners.
The anti-fouling program aims to identify marine natural products that inhibit the settlement of tunicate larvae and thus offer protection for the mussel and oyster industries. The production methods under development involve a search for bacterial sources of bioactive compounds isolated from marine invertebrates, and the cloning of biosynthetic genes. Students, research associates and post doctoral fellows are involved in many of the facets of marine natural products research including: synthesis, isolation & characterization, microbiology and molecular biology.
Pseudopterosins
The pseudopterosins are a family of diterpene glycosides isolated from the gorgonian Pseudopterogorgia elisabethae. To date, 26 derivatives have been identified (PsA – PsZ) and in most cases, pseudopterosins represent 2-5% of the crude extract. The pseudopterosins are anti-inflammatory and analgesic agents with potencies superior to that of existing drugs such as indomethacin in mouse ear models. They are not active against PLA2, cyclooxygenase and cytokine release or as regulators of adhesion molecules. Evidence suggests the pseudopterosins block eicosanoid release rather than biosynthesis in murine macrophages. Recent data from the Jacobs laboratory (UCSB) indicates that pseudopterosins inhibit inflammation by a novel mechanism suggesting that these metabolites represent a novel class of anti-inflammatory agent. Importantly, one of the pseudopterosins has a substantial commercial market as an additive in personal care products and a simple derivative of pseudopterosin A, methopterosin, has successfully completed a Phase II clinical trial as a topical anti-inflammatory agent.
We have a long-standing interest in the biosynthesis of these marine metabolites. We have elucidated the biosynthetic origin of pseudopterosins from geranylgeranyl diphosphate through a series of radiolabeling experiments as well as detailed NMR-directed investigations (Coleman and Kerr 2000, Kohl and Kerr 2003, Ferns and Kerr 2005a, Ferns and Kerr 2005b, Kerr et al. 2006). One of the key steps in the production of the pseudopterosins (and all terpenes) is the cyclization of the appropriate polyprenyl diphosphate. Knowledge of the structure of the cyclase product involved in pseudopterosin biosynthesis provided us with an assay to purify the enzyme responsible for this transformation. This enzyme (elisabethatriene synthase) has been purified to homogeneity (Kohl and Kerr 2004, Brueck and Kerr 2006). A biosynthetic question that is currently under investigation is whether pseudopterosins are produced by the invertebrate host or an associated microbe.
Projects
Find the the last data on your favorite Projects...
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The advancements on the main project in the KerrLab are summarized here. Find the the last data on your favorite Projects: EC, Chem_lab, Synthesis, PE, Microbial diversity, and Microbial Drug Discovery.
Eleutherobin
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| Erythropodium caribaeorum |
Erythropodium caribaeorum (polyps open) |
Eleutherobin is a diterpene glycoside that has been shown to be a potent cancer cell inhibitor with an IC50 similar to that of paclitaxel (Taxol®). Assays in the National Cancer Institute’s 60 cell line panel showed a 100-fold greater potency over the mean cytotoxicity towards breast, renal, ovarian and lung cancer cell lines. It has also been demonstrated that eleutherobin is active in paclitaxel-resistant cancer cell lines. Significantly, eleutherobin was found to stabilize microtubules by competing for the paclitaxel binding site. The initial discovery of eleutherobin was from an examination of the soft coral Eleutherobia sp. however, development of this drug was severely hampered as no further samples of the coral could be obtained. Eleutherobin and a series of related compounds were subsequently isolated from the Caribbean gorgonian coral Erythropodium caribaeorum.
The sarcodictyins are diterpenes that are closely related to eleutherobin and have been isolated from a number of corals including: Eleutherobia aurea from South Africa , Bellonella albiflora from Japan , Sarcodictyon roseum from the Mediterranean, as well as E. caribaeorum from the Caribbean . The sarcodictyins have been shown to exhibit significant cytotoxicity to various cancer cell lines yet not at the levels of eleutherobin.
A current project in our research group is focused on elucidating the biosynthetic origin of the eleutherobin family of diterpenes. Within our microbiology program, we are also using a variety of culture dependent and culture independent methods to assess the microbial diversity in Erythropodium caribaeorum.
Drug discovery
One major emphasis of our research group is a natural products drug discovery program based on both macroorganisms (invertebrates and algae) and microbes. Collections are from regions in the Caribbean and Atlantic Canada. We generally plan one or two 10 day trips to the Caribbean each year and also collect locally (PEI
Discovery of anti-fouling agents
The Prince Edward Island PEI
Microbial Diversity Studies
We have a variety of ongoing projects aimed at describing the microbial diversity in gorgonians and unusual marine sediments. Culture-dependent and culture-independent techniques are both being employed.