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Discovery of Biologically Active Fungal Metabolites Resulting from An AMC 2019 Plenary Lecture 1 PL1 Discovery of biologically active fungal metabolites resulting from an international, interdisciplinary research scenario Marc Stadler Helmholtz-Centre for Infection Research, Germany Over the past years, we have been able to build up a sustainable, international network with leading researchers from all over the world to explore systematically the mycobiota of tropical countries for their potential to produce novel chemical entities with potential to combat infectious diseases. In addition, we have targeted rare European species that are difficult to culture. Over the past 5 years, these activities have resulted in the discovery of over 150 new bioactive metabolites that were published in over 50 original publications. The key to the success of these projects was actually the collaboration of chemists with leading taxonomists and other biodiversity researchers. Most of the new compounds were isolated from new genera and species that were concurrently discovered in the course of taxonomic studies. Some of the new metabolites discovered have substantial potential for application, even though their evaluation is still in a rather early stage and it may take a long time and substantial efforts and additional funding until they even reach preclinical development. The strategy of this approach will be outlined, also including some highlights from our recent research in an international, interdisciplinary scenario. Asian Mycological Congress 2019 AMC 2019 Plenary Lecture 2 PL2 Cordyceps and cordycipitoid fungi Xingzhong Liu Institute of Microbiology, Chinese Academy of Sciences, China Cordyceps historically comprised over 400 species and some of them are used extensively in traditional Chinese medicine. In the past few decades, the pharmaceutical and cosmetics, health products developed from cordyceps have made great progress of research and development of cordyceps. However, there is different understanding on cordyceps and cordycipitoid fungi between mycologists and Chinese medicine scientists because mycologists emphasize phylogenic relationship while medicinal scientists emphasize medicinal function. Here “cordyceps" is proposed as a common English word to represent the natural or cultivated entities of the fungi on their hosts. The most research progresses are that many new taxa have been discovered in China and other Asia countries and the -omics studies have revealed the mechanisms of evolution and biology of cordycipitoid fungi and their interaction with host insects. In the meanwhile, Chinese cordyceps, a valuable Chinese traditional medicine and national fungus of China, its successful cultivation ex situ by a detailed investigation into the cycle of Thitarodes xiaojinensis infected by Ophiocordyceps sinensis has created a large industry. Breakthroughs in artificial cultivation of Chinese cordyceps will certainly benefit the scientific research, environment protection of Tibet- plateau, human health and social progress. Asian Mycological Congress 2019 AMC 2019 Plenary Lecture 3 PL3 Action Mecanism of Kampo (Traditional Japanese Herbal) Medicines and its Application to Western Drug Development Haruki Yamada DNDi Japan / Kitasato University / Tokyo University of Pharmacy and Life Sciences, Japan Current world health issues are referred to frequent appearance of emerging and re-emerging infectious diseases and the increase of multifactorial diseases under increased population of elderly people and changing life-style and environment, in addition to cancer disease, heart disease and cerebrovascular diseases etc. Traditional Japanese herbal (Kampo) medicines have played important role in the modern medicine of Japan to complement modern western medicines. Kampo medicines have been used as the multi- herbal formula which composed of plant, fungi, animal and mineral-derived traditional herbal medicines. Several important drugs such as ephedrine, quinine, and artemisinin etc. have been discovered from such traditional herbal medicines. Novel immune suppressant, fingolimod has discovered from the constituent of Cordyceps, Isaria sinclaiii, and developed as the drug for multiple sclerosis. During past over 30 years, we have studied to clarify pharmacological actions and active ingredients of Kampo medicines as the multi-ingredients drugs to confirm the clinical efficacy for the evidence and science-based medicines. We also have found anti-influenza viral, anti-malaria, anti-Trypanosoma parasites, anti-depressive, adjuvant, and anti-cancer substances from the plant and fungi-derived herbal medicines by in vitro and in vivo bioassays. These include not only low molecular weight ingredients but also bioactive polysaccharides. In this lecture, I'd like to introduce these our research findings. Our results indicates that Kampo medicines are very effective to recover complicated symptoms caused by disturbance of the body system such as immunological, endocrine and neural systems, and traditional medicines are also useful resource for the development of Western drug and nutraceutical. Asian Mycological Congress 2019 AMC 2019 Keynote Lecture 1 KL1 Some of the missing fungi, hidden right in front of us Jennifer Luangsa-ard Plant Microbe Interaction Research Team, BIOTEC, Thailand The BIOTEC culture collection houses 50,000+ isolates and the largest component are insect fungi with 12,000+ isolates, comprising ca. 25% of the collection. The specimens, which are derived from surveys made from natural forests, community forests and agricultural ecosystems in Thailand, are stored in the BIOTEC Bangkok Herbarium. The herbarium consists of 45,000 specimens with insect fungi representing 47% of the collection. Ultimately these fungi are screened for novel metabolites and enzymes in BIOTEC laboratories as well as assessing potential for sources of biological control candidates. The insect fungi of the collection are mainly the hypocrealean genera contained in three families: Clavicipitaceae, Cordycipitaceae and Ophiocordycipitaceae. Research at BIOTEC has been fundamental in supporting the revision of the group of these hypocrealean insect fungi using molecular phylogenetics. While morphological characterization allows preliminary identification of the family or the genus, species recognition is difficult because of its structural simplicity, lack of distinctive phenotypic variations leading to some species being erroneously classified under one name. Purpose: To unravel cryptic species in insect fungi Methods: DNA barcoding using ITS as well as multi-gene analyses comprising the large subunit of the ribosomal DNA (LSU), partial regions of the elongation factor 1-alpha (tef), the largest and second largest subunits of the RNA polymerase genes (rpb1, rpb2) were used. Morphological studies of important phenotypic characters were done in parallel. Results and conclusions: Initial ITS DNA barcoding shows some isolates belonging to genetically distinct lineages, and multi-gene phylogenies using ITS and LSU rDNA, tef, rpb1, and rpb2 supported these results. Importantly, this work is also linked with traditional morphological based approaches. As a result, many new species and genera have been, and are being, described from Thailand. Asian Mycological Congress 2019 AMC 2019 Keynote Lecture 2 KL2 Genetic characterization of mating system and population diversity in Ustilago esculenta, a smut fungus associated with an oriental vegetable Wei-Chiang Shen1,2) 1)Department of Plant Pathology and Microbiology, National Taiwan University, Taiwan 2)Mycological Society of Taiwan Zizania latifolia is a perennial aquatic plant that belongs to the family Poaceae. On infection with the smut fungus Ustilago esculenta, swollen gall is developed at the basal part of the plant and becomes a favorable vegetable known as “water bamboo, water oat, or jiaobai". Development of edible galls is affected significantly by U. esculenta; however, studies related to its genetic features and infection- related processes are limited. To reveal the mating and population features of U. esculenta, we have extensively isolated strains from the field matierals in Taiwan and Japan. By conducting molecular and genomic studies, we identified three idiomorphs of the mating type locus among collected strains. Screening of meiotic offspring and field strains by multiplex PCR and mating assay, we confirmed the bipolar heterothallic mating system in U. esculenta. The MAT-1 locus of U. esculenta is 552,895 bp, the largest mating type locus reported so far in fungi, and contains 44% repeated sequences. Sequence comparison revealed that U. esculenta MAT-1 shares great gene synteny with other smut fungi and may evolve from a common ancestor with S. reilianum due to the chromosomal translocation of P/R and HD loci with an identified intermediate. To further reveal the genetic diversity of U. esculenta population, 13 simple sequence repeat markers have been developed to screen for field strains. The results revealed that U. esculenta strains are separated into two major clustering groups, i.e. T and MT strains. Additionally, T strains showed higher genetic polymorphism as compared to MT strains. In conclusion, our findings have revealed genetic features of U. esculenta population and sexual production and the information will be utilized for commercial breeding and further studies of detailed mechanism of gall formation. Asian Mycological Congress 2019 AMC 2019 Keynote Lecture 3 KL3 Recent Trends of Mushroom Industry and Mushroom Research in Korea Geon-Sik Seo, Min-Kyung
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