Grant: Discovery Grants Program - Individual

After a billion years of evolution, fungi are the masters of survival. This is, in large part, attributed to their ability to produce diverse arrays of bioactive secondary metabolites. Fungi also produce bioactive polysaccharides and a few have been adopted for use as medicine in Asia. However, this is not the case in the West where polysaccharides are generally considered non-specific and relatively few studies have focused on their structure-function relationship. The temperate coastal rainforests of British Columbia (BC) are home to a high biodiversity of organisms, including fungi. Prior to our study, there have been virtually no studies focusing on exploring bioactive secondary metabolites and polysaccharides from BC macrofungi. We hypothesize that BC macrofungi contain new secondary metabolites and polysaccharides that could be used to interrogate cells to understand biological systems and/or for potential use as pharmaceutical/nutraceutical compounds. We have isolated and biochemically and structurally analysed three novel bioactive polysaccharides, two new secondary metabolites, and four known but unique pentacyclic triterpenoids from Echinodontium tinctorium, a wood-decay fungus found only in the Pacific northwest. Our short-term goals focusing on E. tinctorium include: (1) Investigating biosynthesis of pentacyclic triterpenoids in E. tinctorium using Aspergillus oryzae heterologous expression system, (2) Characterizing E. tinctorium mycelium for secondary metabolite discovery and production, (3) Characterizing E. tinctorium mycelium for bioactive polysaccharide production and continuing with a structure-function relationship study, (4) Investigating the production of bioactive polysaccharides from E. tinctorium using A. oryzae heterologous expression platform. The long-term goals of our research program have both scientific and socio-economic impact. We aim to further develop new tools to: (i) discover novel bioactive compounds from other BC macrofungi, (ii) reveal unknown biosynthetic pathways in fungi, (iii) make discoveries that will inspire and encourage the next generation of Canadian scientists to explore our rich natural resources for useful bioactive compounds, and (iv) help advance polysaccharide science so as to narrow the knowledge gap between traditional medicine and Western medicine. Mining BC macrofungi for novel bioactive compounds has important broader impacts. It will enhance natural product discovery and development from a Canadian natural resource, and therefore, in the long-term it could benefit the forestry, agriculture, nutraceutical and/or pharmaceutical industries and positively impact the Canadian economy. This research and its outcomes will raise awareness of the significance and value of our native fungi and therefore the urgency to preserve Canada's fungi biodiversity. This is fundamentally important given the rapid changes in climate resulting in wildfires that have threatened BC's forest ecosystems.