The understanding of the determinants of yeast tolerance to inhibitory compounds present in
fermentation media at the genetic level is of essential importance for the improvement of
second generation bio-ethanol conversion technology. The aim of this study was to
systematically identify, at a genomic scale, the Saccharomyces cerevisiae genes required for
simultaneous and maximal tolerance to key inhibitors derived from lignocellulose biomass
pre-treatment. Based on the screening of the EUROSCARF haploid mutant collection, 242
and 216 determinants of yeast resistance to inhibitory compounds present in industrial wheat
straw hydrolysate (WSH) and in inhibitor-supplemented synthetic hydrolysate (SH) were
identified, respectively. Twenty-two mutants with deleted genes involved in Oxidative stress
response, Lipid Metabolism, Aminoacid metabolism, Vacuolar acidification, Intracellular
trafficking and protein sorting, Transcription machinery and RNA processing and
Mitochondrial function showed a strong susceptibility phenotype in both WSH and SH, 8 of
them being for the first time identified as conferring resistance to lignocellulose-derived
inhibitors. The intersection of our WSH and SH datasets and those obtained in previous
genome-wide studies on single chemical stress resistance, together with results obtained
during comparative fermentative performance analysis [1], provided data for further
evaluation of the key genes involved in global adaptation to toxic biomass hydrolysates. This
study expands our understanding of the genes and underlying molecular mechanisms that
are directly involved in yeast response to the multiple stresses occurring during lignocellulose
fermentations under industrially relevant conditions
