title: Lichen-forming fungus Caloplaca flavoruscens inhibits transcription factors and chromatin remodeling system in fungi.
abstract: Lichen-forming fungi and extracts derived from them have been used as alternative medicine sources for millennia and recently there has been a renewed interest in their known bioactive properties for anticancer agents, cosmetics and antibiotics. Although lichen-forming fungus-derived compounds are biologically and commercially valuable, few studies have been performed to determine their modes of action. This study used chemical-genetic and chemogenomic high-throughput analyses to gain insight into the modes of action of Caloplaca flavoruscens extracts. High-throughput screening of 575 lichen extracts was performed and 39 extracts were identified which inhibited yeast growth. A C. flavoruscens extract was selected as a promising antifungal and was subjected to genome-wide haploinsufficiency profiling and homozygous profiling assays. These screens revealed that yeast deletion strains lacking Rsc8, Pro1 and Toa2 were sensitive to three concentrations (IC25.5, IC25 and IC50, respectively) of C. flavoruscens extract. Gene-enrichment analysis of the data showed that C. flavoruscens extracts appear to perturb transcription and chromatin remodeling.
authors.affiliation: Division of Applied Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: Department of Plant Medicine and Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea.
authors.forename: Jaeyul
authors.initials: J
authors.lastname: Cha
authors.affiliation: Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z3, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chiang
authors.affiliation: Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z3, Canada.
authors.forename: Grant
authors.initials: G
authors.lastname: Tran
authors.affiliation: Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z3, Canada.
authors.forename: Corey
authors.initials: C
authors.lastname: Nislow
authors.affiliation: Korean Lichen Research Institute, Suncheon National University, Suncheon 57922, Republic of Korea.
authors.forename: Jae-Seoun
authors.initials: JS
authors.lastname: Hur
authors.affiliation: Division of Applied Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea Department of Plant Medicine and Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea kwak@gnu.ac.kr.
authors.forename: Youn-Sig
authors.initials: YS
authors.lastname: Kwak
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects*; D057895:Haploinsufficiency; D006720:Homozygote; D008011:Lichens / Q000737:chemistry* / Q000378:metabolism; D012440:Saccharomyces / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D014157:Transcription Factors / Q000037:antagonists & inhibitors*
chemical_list: D000935:Antifungal Agents; D014157:Transcription Factors
keywords: HIP-HOP assay; antifungal; lichen extract