Current Projects

 

The impact of natural products on modern society is indisputable given their importance to medicine. As one example, 42% of anticancer and 47% of anti-infective agents introduced over the past 25 years are natural products. While remarkable discoveries have been made, the rate of natural product discovery has declined in recent years, profoundly affecting the development of new therapeutics and the related pharmaceutical and biotechnology industries. The general aim of many projects in our lab is to conduct research in natural products chemistry and associated microbiology and genetics to develop innovative methods to improve natural product discovery from microbes of marine origin.

 

 

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.

Microbial Diversity

 

Microbes (bacteria and fungi) are the source of all our natural products investigations and are obtained from a wide diversity of marine habitats.  The marine environment represents an underexplored resource for microbial natural product discovery thus improving the likelihood of isolating new compounds.  We are interested in projects directed at assessing microbial diversity using both culture independent and culture dependent methods.  As is evident from the Field Work tab on this web page, we have on-going collection programs in Canada’s Arctic, Colombia, the Mediterranean, the Black Sea, The Bahamas as well as Atlantic Canada. 
 

 

Accessing Cryptic Natural Product Biosynthetic Pathways

Through funding from NSERC, we have a number of student and postdoc projects that seek to develop new methods for the isolation of marine-derived microbes thus allowing access to new sources of natural products.  Further, this research program aims to develop new methods to induce natural product production in microbial fermentation and seeks to develop a new chemical tool to efficiently identify new natural products from large sets of complex mixtures.  Lastly, antimicrobial assays of relevance to veterinary medicine will be used to guide the isolation and characterization of new natural products.  Overall, this research program will develop research methods that will enhance the rate of discovery of new bioactive natural products.

 

 

 

 

 

 

 

 

Marine Microbes as a New Source of Ingredients for the Personal Care Industry

 

This project represents an exciting collaboration between our group at UPEI, Nautilus Biosciences Canada and Croda International, a world leader in specialty chemicals.  The collaboration aims to harness the chemical production capabilities of microbes of marine origin for the sustainable production of active ingredients in personal care products. To achieve this goal, we will expand the existing marine microbial collection (the Marine Natural Products Bank, MNPB) through collections of marine sediment, algae and invertebrates in diverse geographic locations.  Microbes will be purified from these samples and fermented under conditions designed to produce natural products with specific properties.  Specifically, extracts of cultured microbes will be tested for the presence of biosurfactants, bioemulsifiers, antimicrobial agents, biofilm dispersants, UV protectants, antioxidants and keratinases.  These activities have been identified as key to personal care products being developed by Nautilus partner Croda. 

 

 

 

 

 

Identification of novel enzymes involved in the breakdown of plant fibre to be used in the development of a ruminant feed additive

 

 

In collaboration with Nautilus and AB Vista, we are screening our marine microbial library for enzymes with applications as a feed additive for the ruminant feed industry which can increase fibre digestion.  The overall goal of this project is to identify new novel xylanase, cellulase and endoglucanase activities and accessory enzymes (arabinofuranosidase, xylosidase and glucuronidases) which can be used to develop a new ruminant feed additive which will increase feed efficiency and productivity.