Dr. John Sorensen
Department of Chemistry
University of Manitoba
Winnipeg, Manitoba
Title: “Natural Products Chemistry: Biologically
active molecules from lichens and other fungi.”
Abstract:
Natural products are small molecules produced as the result of secondary metabolism pathways
in microorganisms such as fungi. Our research program is focused on examining in detail the
biosynthesis of natural products produced by various fungal species. One major project involves
screening for new natural products that are produced by soil fungi collected from Northern
Manitoba. This bioprospecting is beginning to show some promise as a source of bioactive
molecules and the structures of some of the natural products isolated to date will be presented.
Our other major research program involves examining the polyketide metabolites produced by
species of lichen fungi native to Northern Manitoba. Lichens are a symbiotic association
between a fungal and an algal partner. These slow growing organisms are a rich source of
secondary metabolites, many of which have a demonstrated biological activity. Our main focus
at present is the biosynthesis of usnic acid, produced by various species of Cladonia lichen.
Usnic acid has shown activity against cancer cell lines and is used commercially as an
antibiotic. This metabolite is a product of the polyketide pathway and it appears that two
enzymatic processes are necessary for the formation of usnic
O
OH O
acid. An initial assembly step, presumably catalyzed by a H3C
H3C
CH3
polyketide
synthase,
forms
the
key
intermediate,
methylphloracetophenone from acetate-derived building blocks. HO
OH
The final step in usnic acid biosynthesis is an enzyme catalyzed
O
O
oxidative dimerization of methylphloracetophenone. Our gaol is to
CH3 Usnic Acid
characterize the enzymes responsible for each step in usnic acid
biosynthesis using a molecular biology approach. Our efforts towards cloning the usinc acid
polyketide synthase gene will be presented. We have also devised an efficient synthesis of
methylphloracetophenone, providing us a substrate for characterization of the oxidative enzyme.