초록
<P><B>Background</B></P><P>The understanding of the molecular basis of yeast tolerance to ethanol may guide the design of rational strategies to increase process performance in industrial alcoholic fermentations. A set of 21 genes encoding multidrug transporters from the ATP-Binding Cassette (ABC) Superfamily and Major Facilitator Superfamily (MFS) in <I>S. cerevisiae</I> were scrutinized for a role in ethanol stress resistance.</P><P><B>Results</B></P><P>A yeast multidrug resistance ABC transporter encoded by the <I>PDR18</I> gene, proposed to play a role in the incorporation of ergosterol in the yeast plasma membrane, was found to confer resistance to growth inhibitory concentrations of ethanol. <I>PDR18</I> expression was seen to contribute to decreased <SUP>3</SUP> H-ethanol intracellular concentrations and decreased plasma membrane permeabilization of yeast cells challenged with inhibitory ethanol concentrations. Given the increased tolerance to ethanol of cells expressing <I>PDR18</I>, the final concentration of ethanol produced during high gravity alcoholic fermentation by yeast cells devoid of <I>PDR18</I> was lower than the final ethanol concentration produced by the corresponding parental strain. Moreover, an engineered yeast strain in which the <I>PDR18</I> promoter was replaced in the genome by the stronger <I>PDR5</I> promoter, leading to increased <I>PDR18</I> mRNA levels during alcoholic fermentation, was able to attain a 6 % higher ethanol concentration and a 17 % higher ethanol production yield than the parental strain. The improved fermentative performance of yeast cells over-expressing <I>PDR18</I> was found to correlate with their increased ethanol tolerance and ability to restrain plasma membrane permeabilization induced throughout high gravity fermentation.</P><P><B>Conclusions</B></P><P><I>PDR18</I> gene over-expression increases yeast ethanol tolerance and fermentation performance leading to the production of highly inhibitory concentrations of ethanol. <I>PDR18</I> overexpression in industrial yeast strains appears to be a promising approach to improve alcoholic fermentation performance for sustainable bio-ethanol production.</P>