Searching for Anti-Cancer and Anti-Parasite Leads from Filamentous Fungi PDF
Preview Searching for Anti-Cancer and Anti-Parasite Leads from Filamentous Fungi
Searching for Anti-Cancer and Anti-Parasite Leads from Filamentous Fungi Cedric Pearce, Ph.D Mycosynthetix, Inc. Sao Paulo, Brasil 2014 Outline • basic mycology • history of fungus metabolites • out approach to isolation and characterization • National Cancer Institute funded project • antiparasitic research malaria/leishmaniasis • crop protection work on bioherbicides Basic Mycology - Fungi • Eukaryotes – genetically closer to animals than plants • Heterotrophic aerobes – require organic carbon source • Adapted to many substrates/environments – ubiquitous • 1.5-5 million species – 75,000 described in literature • Talented synthetic chemists – 12,000 unique compounds cataloged • THE MAJORITY OF FUNGI HAVE NEVER BEEN EVALAUTED Fungal Metabolism and Secondary Metabolites substrate nutrients extra cellular enzymes primary metabolism fungal cell organic acids, simple sugars, amino acids secondary metabolism cell components e.g. brefeldin A – P.decumbens e.g. gliotoxin - Aspergillus fumigatus e.g. lentinan - Lentinus edodes 1,200 years of fungal based medicines ten important products From top left to bottom right .... Red yeast rice (800AD), psilocybin (middle ages), penicillin, cephalosporin, LSD, 1,200 years of fungal based medicines ten important products part II From top left to bottom right .... lentinan - Lentinus edodes, cyclosporin, statins, strobilurins, cancidas and finally, Gilenya (approved for MS October 2010) Cherilyn R. Strader, Cedric J. Pearce, and Nicholas H. Oberlies. Fingolimod (FTY720): A Recently Approved Multiple Sclerosis Drug Based on a Fungal Secondary Metabolite. Journal of Natural 6 Products, 2011, 74, 900-907. PMID:21456524; doi: 10.1021/np2000528 240,000 Compounds from Nature High-throughput Profiling of Microbial Extracts Tatsuya Ito, Takamichi Odake, Hideyuki Katoh, Yuichi Yamaguchi, Masahiro Aoki J Nat Prod 2011 74 983-988 •Analysis of 13,000 fungi showed an average of between 1.04 and 1.73 unique compounds per sample. Theoretically... • number of fungi - 1.5 million - Hawkesworth • other ranges up to 5.1 million (Blackwell Am. J. Bot. March 2011 vol. 98 426-438) • number of secondary metabolites • ~ 2 unique compounds per strain studied • up to 30 silent pathways - e.g. polyketides • ~12,000 fungal metabolites in the literature • where are the remaining 3-10 million metabolites?
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