Involvement of Vacuolar Sequestration and Active Transport in Tolerance of Saccharomyces cerevisiae to Hop Iso-?-Acids

Involvement of Vacuolar Sequestration and Active Transport in Tolerance of Saccharomyces cerevisiae to Hop Iso-?-Acids

Hazelwood, L.A.
Walsh, M.C.
Pronk, J.T.
Daran, J.M.

Applied Sciences

Department of Biotechnology

2009-11-13

The hop plant, Humulus lupulus L., has an exceptionally high content of secondary metabolites, the hop -acids, which possess a range of beneficial properties, including antiseptic action. Studies performed on the mode of action of hop iso--acids have hitherto been restricted to lactic acid bacteria. The present study investigated molecular mechanisms of hop iso--acid resistance in the model eukaryote Saccharomyces cerevisiae. Growth inhibition occurred at concentrations of hop iso--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--acid detoxification and tolerance. This screening and further analysis of deletion mutants confirmed that yeast tolerance to hop iso--acids involves three major processes, active proton pumping into the vacuole by the vacuolar-type ATPase to enable vacuolar sequestration of iso--acids and alteration of cell wall structure and, to a lesser extent, active export of iso--acids across the plasma membrane. Furthermore, iso--acids were shown to affect cellular metal homeostasis by acting as strong zinc and iron chelators.

OA-Fund TU Delft

http://resolver.tudelft.nl/uuid:8a0c3d0b-33a1-40d9-bfc6-8dba9ea4a5c8

American Society for Microbiology

00992240

Appl. Envir. Microbiol., January 1, 2010; 76: 318 - 328.

Institutional Repository

journal article

(c) ASM