Y Kwon1, J Cha2, J Chiang3, G Tran3, G Giaever3, C Nislow3, J-S Hur4, Y-S Kwak2. 1. Division of Applied Life Science, Gyeongsang National University, Jinju, Korea. 2. Department of Plant Medicine and Institute of Agriculture & Life Science, Gyeongsang National University, Jinju, Korea. 3. Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada. 4. Korean Lichen Research Institute, Suncheon National University, Suncheon, Korea.
Abstract
AIM: To determine uncovered antifungal activity of lichen-derived compound, vulpinic acid, by using chemical-genetic analyses. METHODS AND RESULTS: Haploinsufficiency and homozygous-profiling assays were performed, revealing that strains lacking GLC7, MET4, RFC2, YAE1 and PRP18 were sensitive to three concentrations (12·5, 25 and 50% of inhibitory concentration) of vulpinic acid and independently validated. To verify inhibition of those genes, cell cycle analysis using flow cytometry was performed and relative expressions were measured. Under vulpinic acid-treated condition, cell cycle was arrested in S and G2/M phases and sensitive strains' relative expressions were significantly lower than the wild type yeast. CONCLUSIONS: Vulpinic acid mainly affects cell cycle, glycogen metabolism, transcription and translation to fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Although lichen-derived compounds are commercially valuable, few studies have determined their modes of action. This study used a chemogenomic approach to gain insight into the mechanisms of one of well-known lichen-derived compound, vulpinic acid.
AIM: To determine uncovered antifungal activity of lichen-derived compound, vulpinic acid, by using chemical-genetic analyses. METHODS AND RESULTS:Haploinsufficiency and homozygous-profiling assays were performed, revealing that strains lacking GLC7, MET4, RFC2, YAE1 and PRP18 were sensitive to three concentrations (12·5, 25 and 50% of inhibitory concentration) of vulpinic acid and independently validated. To verify inhibition of those genes, cell cycle analysis using flow cytometry was performed and relative expressions were measured. Under vulpinic acid-treated condition, cell cycle was arrested in S and G2/M phases and sensitive strains' relative expressions were significantly lower than the wild type yeast. CONCLUSIONS:Vulpinic acid mainly affects cell cycle, glycogen metabolism, transcription and translation to fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Although lichen-derived compounds are commercially valuable, few studies have determined their modes of action. This study used a chemogenomic approach to gain insight into the mechanisms of one of well-known lichen-derived compound, vulpinic acid.
Authors: Sang Ah Yi; Ki Hong Nam; Sil Kim; Hae Min So; Rhim Ryoo; Jeung-Whan Han; Ki Hyun Kim; Jaecheol Lee Journal: Genes (Basel) Date: 2019-12-23 Impact factor: 4.096