The hop plant, Humulus lupulus L., contains an exceptionally high content of secondary metabolites, the hop alpha-acids, which possess a range of beneficial properties including antiseptic action. Studies performed on the mode of action of hop iso-alpha-acids have hitherto been restricted to lactic acid bacteria. The present study investigates molecular mechanisms of hop iso-alpha-acid resistance in the model eukaryote Saccharomyces cerevisiae. Growth inhibition occurred at concentrations of hop iso-alpha-acids that were an order of magnitude higher than those found with hop-tolerant prokaryotes. Chemostat-based transcriptome analysis and phenotype screening of the S. cerevisiae haploid gene deletion collection were used as complementary methods to screen for genes involved in hop iso-alpha-acids detoxification and tolerance. This screening and further analysis of deletion mutants confirmed that yeast tolerance to hop iso-alpha-acids involves three major processes:, active proton pumping into the vacuole by the V-ATPase to enable vacuolar sequestration of iso-alpha-acids and alteration of cell wall structure and to a lesser extend active export of iso-alpha-acids across the plasma membrane. Furthermore, iso-alpha-acids were shown to affect cellular metal homeostasis by acting as strong zinc and iron chelators.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|